ALBERT

All Library Books, journals and Electronic Records Telegrafenberg

X
feed icon rss

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
Filter
  • Articles  (673)
  • Models, Molecular  (673)
  • 2010-2014  (673)
  • 1950-1954
  • Medicine  (673)
Collection
  • Articles  (673)
Source
Keywords
Publisher
Years
Year
Journal
Topic
  • 1
    facet.materialart.
    Unknown
    The structural basis for autonomous dimerization of the pre-T-cell antigen receptor (2010)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2010-10-15
    Description: The pre-T-cell antigen receptor (pre-TCR), expressed by immature thymocytes, has a pivotal role in early T-cell development, including TCR beta-selection, survival and proliferation of CD4(-)CD8(-) double-negative thymocytes, and subsequent alphabeta T-cell lineage differentiation. Whereas alphabetaTCR ligation by the peptide-loaded major histocompatibility complex initiates T-cell signalling, pre-TCR-induced signalling occurs by means of a ligand-independent dimerization event. The pre-TCR comprises an invariant alpha-chain (pre-Talpha) that pairs with any TCR beta-chain (TCRbeta) following successful TCR beta-gene rearrangement. Here we provide the basis of pre-Talpha-TCRbeta assembly and pre-TCR dimerization. The pre-Talpha chain comprised a single immunoglobulin-like domain that is structurally distinct from the constant (C) domain of the TCR alpha-chain; nevertheless, the mode of association between pre-Talpha and TCRbeta mirrored that mediated by the Calpha-Cbeta domains of the alphabetaTCR. The pre-TCR had a propensity to dimerize in solution, and the molecular envelope of the pre-TCR dimer correlated well with the observed head-to-tail pre-TCR dimer. This mode of pre-TCR dimerization enabled the pre-Talpha domain to interact with the variable (V) beta domain through residues that are highly conserved across the Vbeta and joining (J) beta gene families, thus mimicking the interactions at the core of the alphabetaTCR's Valpha-Vbeta interface. Disruption of this pre-Talpha-Vbeta dimer interface abrogated pre-TCR dimerization in solution and impaired pre-TCR expression on the cell surface. Accordingly, we provide a mechanism of pre-TCR self-association that allows the pre-Talpha chain to simultaneously 'sample' the correct folding of both the V and C domains of any TCR beta-chain, regardless of its ultimate specificity, which represents a critical checkpoint in T-cell development. This unusual dual-chaperone-like sensing function of pre-Talpha represents a unique mechanism in nature whereby developmental quality control regulates the expression and signalling of an integral membrane receptor complex.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pang, Siew Siew -- Berry, Richard -- Chen, Zhenjun -- Kjer-Nielsen, Lars -- Perugini, Matthew A -- King, Glenn F -- Wang, Christina -- Chew, Sock Hui -- La Gruta, Nicole L -- Williams, Neal K -- Beddoe, Travis -- Tiganis, Tony -- Cowieson, Nathan P -- Godfrey, Dale I -- Purcell, Anthony W -- Wilce, Matthew C J -- McCluskey, James -- Rossjohn, Jamie -- England -- Nature. 2010 Oct 14;467(7317):844-8. doi: 10.1038/nature09448.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Protein Crystallography Unit, Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Clayton, Victoria 3800, Australia.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20944746" target="_blank"〉PubMed〈/a〉
    Keywords: Crystallography, X-Ray ; Gene Rearrangement, T-Lymphocyte/genetics ; Humans ; Models, Molecular ; Mutation ; Protein Folding ; *Protein Multimerization ; Protein Structure, Tertiary ; Receptors, Antigen, T-Cell/*chemistry/genetics/*metabolism ; Receptors, Antigen, T-Cell, alpha-beta/chemistry/metabolism ; Signal Transduction ; Solutions ; T-Lymphocytes/cytology/immunology/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 2
    facet.materialart.
    Unknown
    Active site remodelling accompanies thioester bond formation in the SUMO E1 (2010)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2010-02-19
    Description: E1 enzymes activate ubiquitin (Ub) and ubiquitin-like (Ubl) proteins in two steps by carboxy-terminal adenylation and thioester bond formation to a conserved catalytic cysteine in the E1 Cys domain. The structural basis for these intermediates remains unknown. Here we report crystal structures for human SUMO E1 in complex with SUMO adenylate and tetrahedral intermediate analogues at 2.45 and 2.6 A, respectively. These structures show that side chain contacts to ATP.Mg are released after adenylation to facilitate a 130 degree rotation of the Cys domain during thioester bond formation that is accompanied by remodelling of key structural elements including the helix that contains the E1 catalytic cysteine, the crossover and re-entry loops, and refolding of two helices that are required for adenylation. These changes displace side chains required for adenylation with side chains required for thioester bond formation. Mutational and biochemical analyses indicate these mechanisms are conserved in other E1s.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2866016/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2866016/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Olsen, Shaun K -- Capili, Allan D -- Lu, Xuequan -- Tan, Derek S -- Lima, Christopher D -- F32 GM075695/GM/NIGMS NIH HHS/ -- F32 GM075695-03/GM/NIGMS NIH HHS/ -- R01 AI068038/AI/NIAID NIH HHS/ -- R01 AI068038-02/AI/NIAID NIH HHS/ -- R01 AI068038-03/AI/NIAID NIH HHS/ -- R01 GM065872/GM/NIGMS NIH HHS/ -- R01 GM065872-09/GM/NIGMS NIH HHS/ -- RR-15301/RR/NCRR NIH HHS/ -- England -- Nature. 2010 Feb 18;463(7283):906-12. doi: 10.1038/nature08765.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Structural Biology, Sloan-Kettering Institute, New York, New York 10065, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20164921" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphate/metabolism ; Amino Acid Sequence ; *Biocatalysis ; Catalytic Domain/*physiology ; Conserved Sequence ; Crystallography, X-Ray ; Cysteine/chemistry/metabolism ; Humans ; Magnesium/metabolism ; Models, Molecular ; Molecular Sequence Data ; Protein Conformation ; SUMO-1 Protein/*chemistry/*metabolism ; Saccharomyces cerevisiae ; Saccharomyces cerevisiae Proteins/metabolism ; Small Ubiquitin-Related Modifier Proteins/metabolism ; Sulfides/*metabolism ; Ubiquitin/metabolism ; Ubiquitin-Activating Enzymes/*chemistry/*metabolism ; Ubiquitins/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 3
    facet.materialart.
    Unknown
    A novel and unified two-metal mechanism for DNA cleavage by type II and IA topoisomerases (2010)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2010-05-21
    Description: Type II topoisomerases are required for the management of DNA tangles and supercoils, and are targets of clinical antibiotics and anti-cancer agents. These enzymes catalyse the ATP-dependent passage of one DNA duplex (the transport or T-segment) through a transient, double-stranded break in another (the gate or G-segment), navigating DNA through the protein using a set of dissociable internal interfaces, or 'gates'. For more than 20 years, it has been established that a pair of dimer-related tyrosines, together with divalent cations, catalyse G-segment cleavage. Recent efforts have proposed that strand scission relies on a 'two-metal mechanism', a ubiquitous biochemical strategy that supports vital cellular processes ranging from DNA synthesis to RNA self-splicing. Here we present the structure of the DNA-binding and cleavage core of Saccharomyces cerevisiae topoisomerase II covalently linked to DNA through its active-site tyrosine at 2.5A resolution, revealing for the first time the organization of a cleavage-competent type II topoisomerase configuration. Unexpectedly, metal-soaking experiments indicate that cleavage is catalysed by a novel variation of the classic two-metal approach. Comparative analyses extend this scheme to explain how distantly-related type IA topoisomerases cleave single-stranded DNA, unifying the cleavage mechanisms for these two essential enzyme families. The structure also highlights a hitherto undiscovered allosteric relay that actuates a molecular 'trapdoor' to prevent subunit dissociation during cleavage. This connection illustrates how an indispensable chromosome-disentangling machine auto-regulates DNA breakage to prevent the aberrant formation of mutagenic and cytotoxic genomic lesions.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2882514/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2882514/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schmidt, Bryan H -- Burgin, Alex B -- Deweese, Joseph E -- Osheroff, Neil -- Berger, James M -- CA077373/CA/NCI NIH HHS/ -- GM033944/GM/NIGMS NIH HHS/ -- GM053960/GM/NIGMS NIH HHS/ -- GM08295/GM/NIGMS NIH HHS/ -- R01 CA077373/CA/NCI NIH HHS/ -- R01 CA077373-11S1/CA/NCI NIH HHS/ -- R01 CA077373-12/CA/NCI NIH HHS/ -- R01 GM033944/GM/NIGMS NIH HHS/ -- T32 CA009592/CA/NCI NIH HHS/ -- T32CA09592/CA/NCI NIH HHS/ -- England -- Nature. 2010 Jun 3;465(7298):641-4. doi: 10.1038/nature08974.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Cell Biology, University of California, Berkeley, California 94720, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20485342" target="_blank"〉PubMed〈/a〉
    Keywords: Allosteric Regulation ; Base Sequence ; Catalytic Domain ; Crystallography, X-Ray ; DNA/*chemistry/genetics/*metabolism ; DNA Topoisomerases, Type I/*chemistry/*metabolism ; DNA Topoisomerases, Type II/*chemistry/*metabolism ; Kinetics ; Models, Molecular ; Molecular Sequence Data ; Saccharomyces cerevisiae/*enzymology ; Tyrosine
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 4
    facet.materialart.
    Unknown
    Coupled chaperone action in folding and assembly of hexadecameric Rubisco (2010)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2010-01-16
    Description: Form I Rubisco (ribulose 1,5-bisphosphate carboxylase/oxygenase), a complex of eight large (RbcL) and eight small (RbcS) subunits, catalyses the fixation of atmospheric CO(2) in photosynthesis. The limited catalytic efficiency of Rubisco has sparked extensive efforts to re-engineer the enzyme with the goal of enhancing agricultural productivity. To facilitate such efforts we analysed the formation of cyanobacterial form I Rubisco by in vitro reconstitution and cryo-electron microscopy. We show that RbcL subunit folding by the GroEL/GroES chaperonin is tightly coupled with assembly mediated by the chaperone RbcX(2). RbcL monomers remain partially unstable and retain high affinity for GroEL until captured by RbcX(2). As revealed by the structure of a RbcL(8)-(RbcX(2))(8) assembly intermediate, RbcX(2) acts as a molecular staple in stabilizing the RbcL subunits as dimers and facilitates RbcL(8) core assembly. Finally, addition of RbcS results in RbcX(2) release and holoenzyme formation. Specific assembly chaperones may be required more generally in the formation of complex oligomeric structures when folding is closely coupled to assembly.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Liu, Cuimin -- Young, Anna L -- Starling-Windhof, Amanda -- Bracher, Andreas -- Saschenbrecker, Sandra -- Rao, Bharathi Vasudeva -- Rao, Karnam Vasudeva -- Berninghausen, Otto -- Mielke, Thorsten -- Hartl, F Ulrich -- Beckmann, Roland -- Hayer-Hartl, Manajit -- England -- Nature. 2010 Jan 14;463(7278):197-202. doi: 10.1038/nature08651.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cellular Biochemistry, Max Planck Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20075914" target="_blank"〉PubMed〈/a〉
    Keywords: Bacterial Proteins/chemistry/metabolism ; Chaperonin 10/metabolism ; Chaperonin 60/metabolism ; Cryoelectron Microscopy ; Holoenzymes/chemistry/metabolism ; Models, Molecular ; Molecular Chaperones/chemistry/*metabolism ; Protein Binding ; *Protein Folding ; *Protein Multimerization ; Protein Structure, Quaternary ; Protein Structure, Tertiary ; Ribulose-Bisphosphate Carboxylase/*chemistry/*metabolism/ultrastructure ; Synechococcus/*chemistry/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 5
    facet.materialart.
    Unknown
    The folding cooperativity of a protein is controlled by its chain topology (2010)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2010-05-25
    Description: The three-dimensional structures of proteins often show a modular architecture comprised of discrete structural regions or domains. Cooperative communication between these regions is important for catalysis, regulation and efficient folding; lack of coupling has been implicated in the formation of fibrils and other misfolding pathologies. How different structural regions of a protein communicate and contribute to a protein's overall energetics and folding, however, is still poorly understood. Here we use a single-molecule optical tweezers approach to induce the selective unfolding of particular regions of T4 lysozyme and monitor the effect on other regions not directly acted on by force. We investigate how the topological organization of a protein (the order of structural elements along the sequence) affects the coupling and folding cooperativity between its domains. To probe the status of the regions not directly subjected to force, we determine the free energy changes during mechanical unfolding using Crooks' fluctuation theorem. We pull on topological variants (circular permutants) and find that the topological organization of the polypeptide chain critically determines the folding cooperativity between domains and thus what parts of the folding/unfolding landscape are explored. We speculate that proteins may have evolved to select certain topologies that increase coupling between regions to avoid areas of the landscape that lead to kinetic trapping and misfolding.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2911970/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2911970/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shank, Elizabeth A -- Cecconi, Ciro -- Dill, Jesse W -- Marqusee, Susan -- Bustamante, Carlos -- GM 32543/GM/NIGMS NIH HHS/ -- GM 50945/GM/NIGMS NIH HHS/ -- R01 GM050945/GM/NIGMS NIH HHS/ -- R01 GM050945-17/GM/NIGMS NIH HHS/ -- England -- Nature. 2010 Jun 3;465(7298):637-40. doi: 10.1038/nature09021. Epub 2010 May 23.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular & Cell Biology, University of California, Berkeley, California 94720, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20495548" target="_blank"〉PubMed〈/a〉
    Keywords: Allosteric Regulation ; Bacteriophage T4/*enzymology ; Models, Molecular ; Mutant Proteins/chemistry/genetics/metabolism ; Optical Tweezers ; Probability ; Protein Denaturation ; *Protein Folding ; Protein Structure, Tertiary ; Viral Proteins/*chemistry/genetics/*metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 6
    facet.materialart.
    Unknown
    Jasmonate perception by inositol-phosphate-potentiated COI1-JAZ co-receptor (2010)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2010-10-12
    Description: Jasmonates are a family of plant hormones that regulate plant growth, development and responses to stress. The F-box protein CORONATINE INSENSITIVE 1 (COI1) mediates jasmonate signalling by promoting hormone-dependent ubiquitylation and degradation of transcriptional repressor JAZ proteins. Despite its importance, the mechanism of jasmonate perception remains unclear. Here we present structural and pharmacological data to show that the true Arabidopsis jasmonate receptor is a complex of both COI1 and JAZ. COI1 contains an open pocket that recognizes the bioactive hormone (3R,7S)-jasmonoyl-l-isoleucine (JA-Ile) with high specificity. High-affinity hormone binding requires a bipartite JAZ degron sequence consisting of a conserved alpha-helix for COI1 docking and a loop region to trap the hormone in its binding pocket. In addition, we identify a third critical component of the jasmonate co-receptor complex, inositol pentakisphosphate, which interacts with both COI1 and JAZ adjacent to the ligand. Our results unravel the mechanism of jasmonate perception and highlight the ability of F-box proteins to evolve as multi-component signalling hubs.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2988090/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2988090/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sheard, Laura B -- Tan, Xu -- Mao, Haibin -- Withers, John -- Ben-Nissan, Gili -- Hinds, Thomas R -- Kobayashi, Yuichi -- Hsu, Fong-Fu -- Sharon, Michal -- Browse, John -- He, Sheng Yang -- Rizo, Josep -- Howe, Gregg A -- Zheng, Ning -- P30 DK056341/DK/NIDDK NIH HHS/ -- P30 DK056341-10/DK/NIDDK NIH HHS/ -- R01 AI068718/AI/NIAID NIH HHS/ -- R01 AI068718-04/AI/NIAID NIH HHS/ -- R01 CA107134/CA/NCI NIH HHS/ -- R01 CA107134-07/CA/NCI NIH HHS/ -- R01 GM057795/GM/NIGMS NIH HHS/ -- R01 GM057795-12/GM/NIGMS NIH HHS/ -- R01AI068718/AI/NIAID NIH HHS/ -- R01GM57795/GM/NIGMS NIH HHS/ -- T32 GM07270/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2010 Nov 18;468(7322):400-5. doi: 10.1038/nature09430. Epub 2010 Oct 6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmacology, Box 357280, University of Washington, Seattle, Washington 98195, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20927106" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Amino Acids/chemistry/metabolism ; Arabidopsis/chemistry/metabolism ; Arabidopsis Proteins/*chemistry/*metabolism ; Binding Sites ; Crystallography, X-Ray ; Cyclopentanes/chemistry/*metabolism ; F-Box Proteins/chemistry/metabolism ; Indenes/chemistry/metabolism ; Inositol Phosphates/*metabolism ; Isoleucine/analogs & derivatives/chemistry/metabolism ; Models, Molecular ; Molecular Sequence Data ; Oxylipins/chemistry/*metabolism ; Peptide Fragments/chemistry/metabolism ; Plant Growth Regulators/chemistry/*metabolism ; Protein Binding ; Protein Structure, Tertiary ; Repressor Proteins/*chemistry/*metabolism ; Signal Transduction
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 7
    facet.materialart.
    Unknown
    Coherently wired light-harvesting in photosynthetic marine algae at ambient temperature (2010)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2010-02-05
    Description: Photosynthesis makes use of sunlight to convert carbon dioxide into useful biomass and is vital for life on Earth. Crucial components for the photosynthetic process are antenna proteins, which absorb light and transmit the resultant excitation energy between molecules to a reaction centre. The efficiency of these electronic energy transfers has inspired much work on antenna proteins isolated from photosynthetic organisms to uncover the basic mechanisms at play. Intriguingly, recent work has documented that light-absorbing molecules in some photosynthetic proteins capture and transfer energy according to quantum-mechanical probability laws instead of classical laws at temperatures up to 180 K. This contrasts with the long-held view that long-range quantum coherence between molecules cannot be sustained in complex biological systems, even at low temperatures. Here we present two-dimensional photon echo spectroscopy measurements on two evolutionarily related light-harvesting proteins isolated from marine cryptophyte algae, which reveal exceptionally long-lasting excitation oscillations with distinct correlations and anti-correlations even at ambient temperature. These observations provide compelling evidence for quantum-coherent sharing of electronic excitation across the 5-nm-wide proteins under biologically relevant conditions, suggesting that distant molecules within the photosynthetic proteins are 'wired' together by quantum coherence for more efficient light-harvesting in cryptophyte marine algae.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Collini, Elisabetta -- Wong, Cathy Y -- Wilk, Krystyna E -- Curmi, Paul M G -- Brumer, Paul -- Scholes, Gregory D -- England -- Nature. 2010 Feb 4;463(7281):644-7. doi: 10.1038/nature08811.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry, Institute for Optical Sciences and Centre for Quantum Information and Quantum Control, University of Toronto, 80 St George Street, Toronto, Ontario, M5S 3H6 Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20130647" target="_blank"〉PubMed〈/a〉
    Keywords: Algal Proteins/chemistry/metabolism ; Cryptophyta/*metabolism/*radiation effects ; *Light ; Light-Harvesting Protein Complexes/chemistry/metabolism ; Models, Molecular ; Photons ; Photosynthesis/physiology/*radiation effects ; Protein Conformation ; Quantum Theory ; *Temperature
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 8
    facet.materialart.
    Unknown
    Structural basis for the suppression of skin cancers by DNA polymerase eta (2010)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2010-06-26
    Description: DNA polymerase eta (Poleta) is unique among eukaryotic polymerases in its proficient ability for error-free replication through ultraviolet-induced cyclobutane pyrimidine dimers, and inactivation of Poleta (also known as POLH) in humans causes the variant form of xeroderma pigmentosum (XPV). We present the crystal structures of Saccharomyces cerevisiae Poleta (also known as RAD30) in ternary complex with a cis-syn thymine-thymine (T-T) dimer and with undamaged DNA. The structures reveal that the ability of Poleta to replicate efficiently through the ultraviolet-induced lesion derives from a simple and yet elegant mechanism, wherein the two Ts of the T-T dimer are accommodated in an active site cleft that is much more open than in other polymerases. We also show by structural, biochemical and genetic analysis that the two Ts are maintained in a stable configuration in the active site via interactions with Gln 55, Arg 73 and Met 74. Together, these features define the basis for Poleta's action on ultraviolet-damaged DNA that is crucial in suppressing the mutagenic and carcinogenic consequences of sun exposure, thereby reducing the incidence of skin cancers in humans.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3030469/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3030469/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Silverstein, Timothy D -- Johnson, Robert E -- Jain, Rinku -- Prakash, Louise -- Prakash, Satya -- Aggarwal, Aneel K -- P30 EB009998/EB/NIBIB NIH HHS/ -- R01 CA107650/CA/NCI NIH HHS/ -- R01 CA107650-39/CA/NCI NIH HHS/ -- R01 ES017767/ES/NIEHS NIH HHS/ -- R01 ES017767-01/ES/NIEHS NIH HHS/ -- England -- Nature. 2010 Jun 24;465(7301):1039-43. doi: 10.1038/nature09104.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Structural and Chemical Biology, Mount Sinai School of Medicine, Box 1677, 1425 Madison Avenue, New York, New York 10029, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20577207" target="_blank"〉PubMed〈/a〉
    Keywords: Biocatalysis ; Catalytic Domain ; Crystallography, X-Ray ; DNA/chemistry/metabolism ; DNA Damage ; DNA-Directed DNA Polymerase/*chemistry/genetics/*metabolism ; Humans ; Kinetics ; Models, Molecular ; Mutation, Missense ; Nucleic Acid Conformation ; Protein Structure, Tertiary ; Pyrimidine Dimers/chemistry/metabolism ; Saccharomyces cerevisiae/*enzymology/genetics ; Skin Neoplasms/*enzymology/genetics ; Structure-Activity Relationship ; Xeroderma Pigmentosum/enzymology/genetics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 9
    facet.materialart.
    Unknown
    A redox switch in angiotensinogen modulates angiotensin release (2010)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2010-10-12
    Description: Blood pressure is critically controlled by angiotensins, which are vasopressor peptides specifically released by the enzyme renin from the tail of angiotensinogen-a non-inhibitory member of the serpin family of protease inhibitors. Although angiotensinogen has long been regarded as a passive substrate, the crystal structures solved here to 2.1 A resolution show that the angiotensin cleavage site is inaccessibly buried in its amino-terminal tail. The conformational rearrangement that makes this site accessible for proteolysis is revealed in our 4.4 A structure of the complex of human angiotensinogen with renin. The co-ordinated changes involved are seen to be critically linked by a conserved but labile disulphide bridge. Here we show that the reduced unbridged form of angiotensinogen is present in the circulation in a near 40:60 ratio with the oxidized sulphydryl-bridged form, which preferentially interacts with receptor-bound renin. We propose that this redox-responsive transition of angiotensinogen to a form that will more effectively release angiotensin at a cellular level contributes to the modulation of blood pressure. Specifically, we demonstrate the oxidative switch of angiotensinogen to its more active sulphydryl-bridged form in the maternal circulation in pre-eclampsia-the hypertensive crisis of pregnancy that threatens the health and survival of both mother and child.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3024006/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3024006/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhou, Aiwu -- Carrell, Robin W -- Murphy, Michael P -- Wei, Zhenquan -- Yan, Yahui -- Stanley, Peter L D -- Stein, Penelope E -- Broughton Pipkin, Fiona -- Read, Randy J -- 082961/Wellcome Trust/United Kingdom -- BS/05/002/18361/British Heart Foundation/United Kingdom -- MC_U105663142/Medical Research Council/United Kingdom -- PG/08/041/24818/British Heart Foundation/United Kingdom -- PG/09/072/27945/British Heart Foundation/United Kingdom -- British Heart Foundation/United Kingdom -- Medical Research Council/United Kingdom -- Wellcome Trust/United Kingdom -- England -- Nature. 2010 Nov 4;468(7320):108-11. doi: 10.1038/nature09505. Epub 2010 Oct 6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Haematology, Cambridge Institute for Medical Research, University of Cambridge, Hills Road, Cambridge CB2 0XY, UK. awz20@cam.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20927107" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Angiotensinogen/blood/*chemistry/*metabolism ; Angiotensins/chemistry/*metabolism/secretion ; Blood Pressure ; Crystallography, X-Ray ; Disulfides/chemistry/metabolism ; Female ; Humans ; Kinetics ; Models, Molecular ; Molecular Sequence Data ; Oxidation-Reduction ; Oxidative Stress ; Pre-Eclampsia/blood/metabolism ; Pregnancy ; Protein Conformation ; *Protein Processing, Post-Translational ; Renin/chemistry/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 10
    facet.materialart.
    Unknown
    Crystal structures of the CusA efflux pump suggest methionine-mediated metal transport (2010)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2010-09-25
    Description: Gram-negative bacteria, such as Escherichia coli, frequently use tripartite efflux complexes in the resistance-nodulation-cell division (RND) family to expel various toxic compounds from the cell. The efflux system CusCBA is responsible for extruding biocidal Cu(I) and Ag(I) ions. No previous structural information was available for the heavy-metal efflux (HME) subfamily of the RND efflux pumps. Here we describe the crystal structures of the inner-membrane transporter CusA in the absence and presence of bound Cu(I) or Ag(I). These CusA structures provide new structural information about the HME subfamily of RND efflux pumps. The structures suggest that the metal-binding sites, formed by a three-methionine cluster, are located within the cleft region of the periplasmic domain. This cleft is closed in the apo-CusA form but open in the CusA-Cu(I) and CusA-Ag(I) structures, which directly suggests a plausible pathway for ion export. Binding of Cu(I) and Ag(I) triggers significant conformational changes in both the periplasmic and transmembrane domains. The crystal structure indicates that CusA has, in addition to the three-methionine metal-binding site, four methionine pairs-three located in the transmembrane region and one in the periplasmic domain. Genetic analysis and transport assays suggest that CusA is capable of actively picking up metal ions from the cytosol, using these methionine pairs or clusters to bind and export metal ions. These structures suggest a stepwise shuttle mechanism for transport between these sites.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2946090/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2946090/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Long, Feng -- Su, Chih-Chia -- Zimmermann, Michael T -- Boyken, Scott E -- Rajashankar, Kanagalaghatta R -- Jernigan, Robert L -- Yu, Edward W -- GM 072014/GM/NIGMS NIH HHS/ -- GM 074027/GM/NIGMS NIH HHS/ -- GM 081680/GM/NIGMS NIH HHS/ -- GM 086431/GM/NIGMS NIH HHS/ -- R01 GM072014/GM/NIGMS NIH HHS/ -- R01 GM074027/GM/NIGMS NIH HHS/ -- R01 GM074027-05/GM/NIGMS NIH HHS/ -- R01 GM086431/GM/NIGMS NIH HHS/ -- R01 GM086431-01A2/GM/NIGMS NIH HHS/ -- RR-15301/RR/NCRR NIH HHS/ -- England -- Nature. 2010 Sep 23;467(7314):484-8. doi: 10.1038/nature09395.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Molecular, Cellular and Developmental Biology Interdepartmental Graduate Program, Iowa State University, Iowa 50011, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20865003" target="_blank"〉PubMed〈/a〉
    Keywords: Apoproteins/chemistry/metabolism ; Binding Sites ; Cell Membrane/metabolism ; Copper/chemistry/*metabolism ; Crystallography, X-Ray ; Cytosol/metabolism ; Escherichia coli/*chemistry ; Escherichia coli Proteins/*chemistry/*metabolism ; Ion Transport ; Membrane Transport Proteins/*chemistry/*metabolism ; Methionine/*metabolism ; Models, Biological ; Models, Molecular ; Periplasm/metabolism ; Protein Structure, Quaternary ; Protein Structure, Tertiary ; Silver/chemistry/*metabolism ; Structure-Activity Relationship
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 11
    facet.materialart.
    Unknown
    Structural basis of semaphorin-plexin signalling (2010)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2010-09-30
    Description: Cell-cell signalling of semaphorin ligands through interaction with plexin receptors is important for the homeostasis and morphogenesis of many tissues and is widely studied for its role in neural connectivity, cancer, cell migration and immune responses. SEMA4D and Sema6A exemplify two diverse vertebrate, membrane-spanning semaphorin classes (4 and 6) that are capable of direct signalling through members of the two largest plexin classes, B and A, respectively. In the absence of any structural information on the plexin ectodomain or its interaction with semaphorins the extracellular specificity and mechanism controlling plexin signalling has remained unresolved. Here we present crystal structures of cognate complexes of the semaphorin-binding regions of plexins B1 and A2 with semaphorin ectodomains (human PLXNB1(1-2)-SEMA4D(ecto) and murine PlxnA2(1-4)-Sema6A(ecto)), plus unliganded structures of PlxnA2(1-4) and Sema6A(ecto). These structures, together with biophysical and cellular assays of wild-type and mutant proteins, reveal that semaphorin dimers independently bind two plexin molecules and that signalling is critically dependent on the avidity of the resulting bivalent 2:2 complex (monomeric semaphorin binds plexin but fails to trigger signalling). In combination, our data favour a cell-cell signalling mechanism involving semaphorin-stabilized plexin dimerization, possibly followed by clustering, which is consistent with previous functional data. Furthermore, the shared generic architecture of the complexes, formed through conserved contacts of the amino-terminal seven-bladed beta-propeller (sema) domains of both semaphorin and plexin, suggests that a common mode of interaction triggers all semaphorin-plexin based signalling, while distinct insertions within or between blades of the sema domains determine binding specificity.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3587840/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3587840/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Janssen, Bert J C -- Robinson, Ross A -- Perez-Branguli, Francesc -- Bell, Christian H -- Mitchell, Kevin J -- Siebold, Christian -- Jones, E Yvonne -- 082301/Wellcome Trust/United Kingdom -- 083111/Wellcome Trust/United Kingdom -- 10976/Cancer Research UK/United Kingdom -- A10976/Cancer Research UK/United Kingdom -- A3964/Cancer Research UK/United Kingdom -- A5261/Cancer Research UK/United Kingdom -- G0700232/Medical Research Council/United Kingdom -- G0700232(82098)/Medical Research Council/United Kingdom -- G0900084/Medical Research Council/United Kingdom -- G9900061/Medical Research Council/United Kingdom -- G9900061(69203)/Medical Research Council/United Kingdom -- Cancer Research UK/United Kingdom -- Medical Research Council/United Kingdom -- Wellcome Trust/United Kingdom -- England -- Nature. 2010 Oct 28;467(7319):1118-22. doi: 10.1038/nature09468. Epub 2010 Sep 26.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Structural Biology, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20877282" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens, CD/chemistry/genetics/metabolism ; Binding Sites ; Cell Adhesion Molecules/*chemistry/genetics/*metabolism ; Cell Communication ; Crystallography, X-Ray ; Humans ; Ligands ; Mice ; Mice, Inbred C57BL ; Models, Molecular ; NIH 3T3 Cells ; Nerve Tissue Proteins/*chemistry/genetics/*metabolism ; Protein Binding ; Protein Structure, Tertiary ; Receptors, Cell Surface/chemistry/genetics/metabolism ; Semaphorins/*chemistry/genetics/*metabolism ; *Signal Transduction ; Structure-Activity Relationship
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 12
    facet.materialart.
    Unknown
    Migrastatin analogues target fascin to block tumour metastasis (2010)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2010-04-16
    Description: Tumour metastasis is the primary cause of death of cancer patients. Development of new therapeutics preventing tumour metastasis is urgently needed. Migrastatin is a natural product secreted by Streptomyces, and synthesized migrastatin analogues such as macroketone are potent inhibitors of metastatic tumour cell migration, invasion and metastasis. Here we show that these migrastatin analogues target the actin-bundling protein fascin to inhibit its activity. X-ray crystal structural studies reveal that migrastatin analogues bind to one of the actin-binding sites on fascin. Our data demonstrate that actin cytoskeletal proteins such as fascin can be explored as new molecular targets for cancer treatment, in a similar manner to the microtubule protein tubulin.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2857318/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2857318/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chen, Lin -- Yang, Shengyu -- Jakoncic, Jean -- Zhang, J Jillian -- Huang, Xin-Yun -- CA136837/CA/NCI NIH HHS/ -- R01 CA136837/CA/NCI NIH HHS/ -- R01 CA136837-01A1/CA/NCI NIH HHS/ -- England -- Nature. 2010 Apr 15;464(7291):1062-6. doi: 10.1038/nature08978.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physiology, Cornell University Weill Medical College, New York, New York 10065, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20393565" target="_blank"〉PubMed〈/a〉
    Keywords: Actins/metabolism ; Animals ; Antineoplastic Agents/chemistry/metabolism/pharmacology/therapeutic use ; Binding Sites/drug effects ; Breast Neoplasms/drug therapy/pathology ; Carrier Proteins/*antagonists & inhibitors/chemistry/genetics/metabolism ; Cell Line, Tumor ; Cell Movement/drug effects ; Crystallography, X-Ray ; Drug Resistance, Neoplasm/genetics ; Female ; Humans ; Lung Neoplasms/prevention & control/secondary ; Macrolides/*chemistry/metabolism/*pharmacology/therapeutic use ; Mice ; Mice, Inbred BALB C ; Mice, Inbred NOD ; Mice, SCID ; Microfilament Proteins/*antagonists & inhibitors/chemistry/genetics/metabolism ; Models, Molecular ; Mutation/genetics ; Neoplasm Invasiveness/pathology/prevention & control ; Neoplasm Metastasis/drug therapy/pathology/*prevention & control ; Piperidones/*chemistry/metabolism/*pharmacology/therapeutic use ; Protein Conformation
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 13
    facet.materialart.
    Unknown
    Neurotransmitter/sodium symporter orthologue LeuT has a single high-affinity substrate site (2010)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2010-12-24
    Description: Neurotransmitter/sodium symporters (NSSs) couple the uptake of neurotransmitter with one or more sodium ions, removing neurotransmitter from the synaptic cleft. NSSs are essential to the function of chemical synapses, are associated with multiple neurological diseases and disorders, and are the targets of therapeutic and illicit drugs. LeuT, a prokaryotic orthologue of the NSS family, is a model transporter for understanding the relationships between molecular mechanism and atomic structure in a broad range of sodium-dependent and sodium-independent secondary transporters. At present there is a controversy over whether there are one or two high-affinity substrate binding sites in LeuT. The first-reported crystal structure of LeuT, together with subsequent functional and structural studies, provided direct evidence for a single, high-affinity, centrally located substrate-binding site, defined as the S1 site. Recent binding, flux and molecular simulation studies, however, have been interpreted in terms of a model where there are two high-affinity binding sites: the central, S1, site and a second, the S2 site, located within the extracellular vestibule. Furthermore, it was proposed that the S1 and S2 sites are allosterically coupled such that occupancy of the S2 site is required for the cytoplasmic release of substrate from the S1 site. Here we address this controversy by performing direct measurement of substrate binding to wild-type LeuT and to S2 site mutants using isothermal titration calorimetry, equilibrium dialysis and scintillation proximity assays. In addition, we perform uptake experiments to determine whether the proposed allosteric coupling between the putative S2 site and the S1 site manifests itself in the kinetics of substrate flux. We conclude that LeuT harbours a single, centrally located, high-affinity substrate-binding site and that transport is well described by a simple, single-substrate kinetic mechanism.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3079577/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3079577/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Piscitelli, Chayne L -- Krishnamurthy, Harini -- Gouaux, Eric -- R37 MH070039/MH/NIMH NIH HHS/ -- R37 MH070039-07/MH/NIMH NIH HHS/ -- R37 MH070039-08/MH/NIMH NIH HHS/ -- T32 DK007680/DK/NIDDK NIH HHS/ -- T32 DK007680-17/DK/NIDDK NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2010 Dec 23;468(7327):1129-32. doi: 10.1038/nature09581.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Molecular Biology, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, Oregon 97239, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21179170" target="_blank"〉PubMed〈/a〉
    Keywords: Binding Sites ; Humans ; Ionophores/pharmacology ; Kinetics ; Leucine/genetics ; Models, Molecular ; Mutation ; Plasma Membrane Neurotransmitter Transport ; Proteins/*chemistry/genetics/*metabolism ; Protein Transport/drug effects ; Valinomycin/pharmacology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 14
    facet.materialart.
    Unknown
    Ribosome dynamics and tRNA movement by time-resolved electron cryomicroscopy (2010)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2010-07-16
    Description: The translocation step of protein synthesis entails large-scale rearrangements of the ribosome-transfer RNA (tRNA) complex. Here we have followed tRNA movement through the ribosome during translocation by time-resolved single-particle electron cryomicroscopy (cryo-EM). Unbiased computational sorting of cryo-EM images yielded 50 distinct three-dimensional reconstructions, showing the tRNAs in classical, hybrid and various novel intermediate states that provide trajectories and kinetic information about tRNA movement through the ribosome. The structures indicate how tRNA movement is coupled with global and local conformational changes of the ribosome, in particular of the head and body of the small ribosomal subunit, and show that dynamic interactions between tRNAs and ribosomal residues confine the path of the tRNAs through the ribosome. The temperature dependence of ribosome dynamics reveals a surprisingly flat energy landscape of conformational variations at physiological temperature. The ribosome functions as a Brownian machine that couples spontaneous conformational changes driven by thermal energy to directed movement.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fischer, Niels -- Konevega, Andrey L -- Wintermeyer, Wolfgang -- Rodnina, Marina V -- Stark, Holger -- England -- Nature. 2010 Jul 15;466(7304):329-33. doi: 10.1038/nature09206.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉3D Electron Cryomicroscopy Group, Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, 37077 Gottingen, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20631791" target="_blank"〉PubMed〈/a〉
    Keywords: Cryoelectron Microscopy ; Escherichia coli ; Kinetics ; Models, Molecular ; Molecular Conformation ; *Movement ; *Protein Biosynthesis ; RNA, Transfer/genetics/*metabolism ; Ribosome Subunits, Large, Bacterial/chemistry/metabolism ; Ribosome Subunits, Small, Bacterial/chemistry/metabolism ; Ribosomes/chemistry/*metabolism ; Temperature ; Thermodynamics ; Time Factors
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 15
    facet.materialart.
    Unknown
    Structural mechanism of C-type inactivation in K(+) channels (2010)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2010-07-09
    Description: Interconversion between conductive and non-conductive forms of the K(+) channel selectivity filter underlies a variety of gating events, from flicker transitions (at the microsecond timescale) to C-type inactivation (millisecond to second timescale). Here we report the crystal structure of the Streptomyces lividans K(+) channel KcsA in its open-inactivated conformation and investigate the mechanism of C-type inactivation gating at the selectivity filter from channels 'trapped' in a series of partially open conformations. Five conformer classes were identified with openings ranging from 12 A in closed KcsA (Calpha-Calpha distances at Thr 112) to 32 A when fully open. They revealed a remarkable correlation between the degree of gate opening and the conformation and ion occupancy of the selectivity filter. We show that a gradual filter backbone reorientation leads first to a loss of the S2 ion binding site and a subsequent loss of the S3 binding site, presumably abrogating ion conduction. These structures indicate a molecular basis for C-type inactivation in K(+) channels.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3033749/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3033749/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cuello, Luis G -- Jogini, Vishwanath -- Cortes, D Marien -- Perozo, Eduardo -- R01 GM057846/GM/NIGMS NIH HHS/ -- R01 GM057846-15/GM/NIGMS NIH HHS/ -- R01-GM57846/GM/NIGMS NIH HHS/ -- England -- Nature. 2010 Jul 8;466(7303):203-8. doi: 10.1038/nature09153.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Molecular Biology, and Institute for Biophysical Dynamics, University of Chicago, Illinois 60637, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20613835" target="_blank"〉PubMed〈/a〉
    Keywords: Bacterial Proteins/*antagonists & inhibitors/*chemistry/metabolism ; Binding Sites ; Crystallography, X-Ray ; Electrons ; *Ion Channel Gating ; Kinetics ; Models, Biological ; Models, Molecular ; Potassium/metabolism ; Potassium Channels/*chemistry/metabolism ; Protein Conformation ; Streptomyces lividans/*chemistry ; Structure-Activity Relationship
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 16
    facet.materialart.
    Unknown
    Two enzymes bound to one transfer RNA assume alternative conformations for consecutive reactions (2010)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2010-10-01
    Description: In most bacteria and all archaea, glutamyl-tRNA synthetase (GluRS) glutamylates both tRNA(Glu) and tRNA(Gln), and then Glu-tRNA(Gln) is selectively converted to Gln-tRNA(Gln) by a tRNA-dependent amidotransferase. The mechanisms by which the two enzymes recognize their substrate tRNA(s), and how they cooperate with each other in Gln-tRNA(Gln) synthesis, remain to be determined. Here we report the formation of the 'glutamine transamidosome' from the bacterium Thermotoga maritima, consisting of tRNA(Gln), GluRS and the heterotrimeric amidotransferase GatCAB, and its crystal structure at 3.35 A resolution. The anticodon-binding body of GluRS recognizes the common features of tRNA(Gln) and tRNA(Glu), whereas the tail body of GatCAB recognizes the outer corner of the L-shaped tRNA(Gln) in a tRNA(Gln)-specific manner. GluRS is in the productive form, as its catalytic body binds to the amino-acid-acceptor arm of tRNA(Gln). In contrast, GatCAB is in the non-productive form: the catalytic body of GatCAB contacts that of GluRS and is located near the acceptor stem of tRNA(Gln), in an appropriate site to wait for the completion of Glu-tRNA(Gln) formation by GluRS. We identified the hinges between the catalytic and anticodon-binding bodies of GluRS and between the catalytic and tail bodies of GatCAB, which allow both GluRS and GatCAB to adopt the productive and non-productive forms. The catalytic bodies of the two enzymes compete for the acceptor arm of tRNA(Gln) and therefore cannot assume their productive forms simultaneously. The transition from the present glutamylation state, with the productive GluRS and the non-productive GatCAB, to the putative amidation state, with the non-productive GluRS and the productive GatCAB, requires an intermediate state with the two enzymes in their non-productive forms, for steric reasons. The proposed mechanism explains how the transamidosome efficiently performs the two consecutive steps of Gln-tRNA(Gln) formation, with a low risk of releasing the unstable intermediate Glu-tRNA(Gln).〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ito, Takuhiro -- Yokoyama, Shigeyuki -- England -- Nature. 2010 Sep 30;467(7315):612-6. doi: 10.1038/nature09411.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biophysics and Biochemistry, Graduate School of Science, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20882017" target="_blank"〉PubMed〈/a〉
    Keywords: Anticodon/genetics ; Biocatalysis ; Crystallography, X-Ray ; Electrophoretic Mobility Shift Assay ; Glutamate-tRNA Ligase/*chemistry/*metabolism ; Models, Molecular ; Molecular Conformation ; Nitrogenous Group Transferases/*chemistry/*metabolism ; Protein Binding ; RNA, Transfer, Gln/biosynthesis/*chemistry/*metabolism ; RNA, Transfer, Glu/chemistry/metabolism ; Staphylococcus aureus/enzymology ; Substrate Specificity ; Thermotoga maritima/*enzymology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 17
    facet.materialart.
    Unknown
    Structural basis of oligomerization in the stalk region of dynamin-like MxA (2010)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2010-04-30
    Description: The interferon-inducible dynamin-like myxovirus resistance protein 1 (MxA; also called MX1) GTPase is a key mediator of cell-autonomous innate immunity against pathogens such as influenza viruses. MxA partially localizes to COPI-positive membranes of the smooth endoplasmic reticulum-Golgi intermediate compartment. At the point of infection, it redistributes to sites of viral replication and promotes missorting of essential viral constituents. It has been proposed that the middle domain and the GTPase effector domain of dynamin-like GTPases constitute a stalk that mediates oligomerization and transmits conformational changes from the G domain to the target structure; however, the molecular architecture of this stalk has remained elusive. Here we report the crystal structure of the stalk of human MxA, which folds into a four-helical bundle. This structure tightly oligomerizes in the crystal in a criss-cross pattern involving three distinct interfaces and one loop. Mutations in each of these interaction sites interfere with native assembly, oligomerization, membrane binding and antiviral activity of MxA. On the basis of these results, we propose a structural model for dynamin oligomerization and stimulated GTP hydrolysis that is consistent with previous structural predictions and has functional implications for all members of the dynamin family.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gao, Song -- von der Malsburg, Alexander -- Paeschke, Susann -- Behlke, Joachim -- Haller, Otto -- Kochs, Georg -- Daumke, Oliver -- England -- Nature. 2010 May 27;465(7297):502-6. doi: 10.1038/nature08972. Epub 2010 Apr 28.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Max-Delbruck-Centrum for Molecular Medicine, Crystallography, Robert-Rossle-Strasse 10, 13125 Berlin, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20428112" target="_blank"〉PubMed〈/a〉
    Keywords: Antiviral Agents/chemistry/metabolism/pharmacology ; Binding Sites ; Cell Line ; Crystallography, X-Ray ; Dynamins/*chemistry/metabolism ; GTP Phosphohydrolases/metabolism ; GTP-Binding Proteins/*chemistry/genetics/*metabolism/pharmacology ; Guanosine Triphosphate/metabolism ; Humans ; Hydrolysis ; Hydrophobic and Hydrophilic Interactions ; Influenza A Virus, H5N1 Subtype/drug effects/physiology ; Models, Molecular ; Myxovirus Resistance Proteins ; Protein Conformation ; *Protein Multimerization ; Virus Replication/drug effects
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 18
    facet.materialart.
    Unknown
    NRMT is an alpha-N-methyltransferase that methylates RCC1 and retinoblastoma protein (2010)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2010-07-30
    Description: The post-translational methylation of alpha-amino groups was first discovered over 30 years ago on the bacterial ribosomal proteins L16 and L33 (refs 1, 2), but almost nothing is known about the function or enzymology of this modification. Several other bacterial and eukaryotic proteins have since been shown to be alpha-N-methylated. However, the Ran guanine nucleotide-exchange factor, RCC1, is the only protein for which any biological function of alpha-N-methylation has been identified. Methylation-defective mutants of RCC1 have reduced affinity for DNA and cause mitotic defects, but further characterization of this modification has been hindered by ignorance of the responsible methyltransferase. All fungal and animal N-terminally methylated proteins contain a unique N-terminal motif, Met-(Ala/Pro/Ser)-Pro-Lys, indicating that they may be targets of the same, unknown enzyme. The initiating Met is cleaved, and the exposed alpha-amino group is mono-, di- or trimethylated. Here we report the discovery of the first alpha-N-methyltransferase, which we named N-terminal RCC1 methyltransferase (NRMT). Substrate docking and mutational analysis of RCC1 defined the NRMT recognition sequence and enabled the identification of numerous new methylation targets, including SET (also known as TAF-I or PHAPII) and the retinoblastoma protein, RB. Knockdown of NRMT recapitulates the multi-spindle phenotype seen with methylation-defective RCC1 mutants, demonstrating the importance of alpha-N-methylation for normal bipolar spindle formation and chromosome segregation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2939154/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2939154/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tooley, Christine E Schaner -- Petkowski, Janusz J -- Muratore-Schroeder, Tara L -- Balsbaugh, Jeremy L -- Shabanowitz, Jeffrey -- Sabat, Michal -- Minor, Wladek -- Hunt, Donald F -- Macara, Ian G -- R01 GM050526/GM/NIGMS NIH HHS/ -- R01 GM050526-17/GM/NIGMS NIH HHS/ -- England -- Nature. 2010 Aug 26;466(7310):1125-8. doi: 10.1038/nature09343.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology, Center for Cell Signaling, University of Virginia School of Medicine, Charlottesville, Virginia 22908, USA. ces5g@virginia.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20668449" target="_blank"〉PubMed〈/a〉
    Keywords: Cell Cycle Proteins/*metabolism ; Cell Line ; Chromosome Segregation ; Gene Knockdown Techniques ; Guanine Nucleotide Exchange Factors/*metabolism ; HeLa Cells ; Histone Chaperones/metabolism ; Humans ; Methyltransferases/chemistry/genetics/*metabolism ; Models, Molecular ; Mutation/genetics ; Nuclear Proteins/*metabolism ; Protein Binding ; Protein Structure, Tertiary ; Retinoblastoma Protein/*metabolism ; Spindle Apparatus/metabolism ; Transcription Factors/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 19
    facet.materialart.
    Unknown
    Structural basis for the photoconversion of a phytochrome to the activated Pfr form (2010)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2010-01-16
    Description: Phytochromes are a collection of bilin-containing photoreceptors that regulate numerous photoresponses in plants and microorganisms through their ability to photointerconvert between a red-light-absorbing, ground state (Pr) and a far-red-light-absorbing, photoactivated state (Pfr). Although the structures of several phytochromes as Pr have been determined, little is known about the structure of Pfr and how it initiates signalling. Here we describe the three-dimensional solution structure of the bilin-binding domain as Pfr, using the cyanobacterial phytochrome from Synechococcus OSB'. Contrary to predictions, light-induced rotation of the A pyrrole ring but not the D ring is the primary motion of the chromophore during photoconversion. Subsequent rearrangements within the protein then affect intradomain and interdomain contact sites within the phytochrome dimer. On the basis of our models, we propose that phytochromes act by propagating reversible light-driven conformational changes in the bilin to altered contacts between the adjacent output domains, which in most phytochromes direct differential phosphotransfer.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2807988/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2807988/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ulijasz, Andrew T -- Cornilescu, Gabriel -- Cornilescu, Claudia C -- Zhang, Junrui -- Rivera, Mario -- Markley, John L -- Vierstra, Richard D -- P41 RR002301/RR/NCRR NIH HHS/ -- P41 RR002301-237748/RR/NCRR NIH HHS/ -- U54 GM074901/GM/NIGMS NIH HHS/ -- U54 GM074901-05/GM/NIGMS NIH HHS/ -- England -- Nature. 2010 Jan 14;463(7278):250-4. doi: 10.1038/nature08671.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genetics and, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20075921" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acids/chemistry/metabolism/radiation effects ; Bacterial Proteins/*chemistry/genetics/metabolism/*radiation effects ; Bile Pigments/chemistry/metabolism/radiation effects ; Binding Sites ; *Light ; Magnetic Resonance Spectroscopy ; Models, Molecular ; Phytochrome/*chemistry/genetics/metabolism/*radiation effects ; Protein Kinases/*chemistry/genetics/metabolism/*radiation effects ; Protein Structure, Tertiary/radiation effects ; Rotation ; Synechococcus/*chemistry/genetics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 20
    facet.materialart.
    Unknown
    Neurological disease mutations compromise a C-terminal ion pathway in the Na(+)/K(+)-ATPase (2010)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2010-08-20
    Description: The Na(+)/K(+)-ATPase pumps three sodium ions out of and two potassium ions into the cell for each ATP molecule that is split, thereby generating the chemical and electrical gradients across the plasma membrane that are essential in, for example, signalling, secondary transport and volume regulation in animal cells. Crystal structures of the potassium-bound form of the pump revealed an intimate docking of the alpha-subunit carboxy terminus at the transmembrane domain. Here we show that this element is a key regulator of a previously unrecognized ion pathway. Current models of P-type ATPases operate with a single ion conduit through the pump, but our data suggest an additional pathway in the Na(+)/K(+)-ATPase between the ion-binding sites and the cytoplasm. The C-terminal pathway allows a cytoplasmic proton to enter and stabilize site III when empty in the potassium-bound state, and when potassium is released the proton will also return to the cytoplasm, thus allowing an overall asymmetric stoichiometry of the transported ions. The C terminus controls the gate to the pathway. Its structure is crucial for pump function, as demonstrated by at least eight mutations in the region that cause severe neurological diseases. This novel model for ion transport by the Na(+)/K(+)-ATPase is established by electrophysiological studies of C-terminal mutations in familial hemiplegic migraine 2 (FHM2) and is further substantiated by molecular dynamics simulations. A similar ion regulation is likely to apply to the H(+)/K(+)-ATPase and the Ca(2+)-ATPase.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Poulsen, Hanne -- Khandelia, Himanshu -- Morth, J Preben -- Bublitz, Maike -- Mouritsen, Ole G -- Egebjerg, Jan -- Nissen, Poul -- England -- Nature. 2010 Sep 2;467(7311):99-102. doi: 10.1038/nature09309. Epub 2010 Aug 15.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉PUMPKIN - Centre for Membrane Pumps in Cells and Disease, Danish National Research Foundation, Department of Molecular Biology, Aarhus University, DK-8000 Aarhus C, Denmark. hp@mb.au.dk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20720542" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Crystallography, X-Ray ; Humans ; *Ion Transport ; Migraine with Aura/genetics/*metabolism ; Models, Molecular ; Molecular Dynamics Simulation ; Oocytes/metabolism ; Potassium/metabolism ; Protons ; Sodium-Potassium-Exchanging ATPase/*chemistry/*metabolism ; Squalus acanthias/metabolism ; Sus scrofa/metabolism ; Xenopus
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 21
    facet.materialart.
    Unknown
    Super-resolution biomolecular crystallography with low-resolution data (2010)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2010-04-09
    Description: X-ray diffraction plays a pivotal role in the understanding of biological systems by revealing atomic structures of proteins, nucleic acids and their complexes, with much recent interest in very large assemblies like the ribosome. As crystals of such large assemblies often diffract weakly (resolution worse than 4 A), we need methods that work at such low resolution. In macromolecular assemblies, some of the components may be known at high resolution, whereas others are unknown: current refinement methods fail as they require a high-resolution starting structure for the entire complex. Determining the structure of such complexes, which are often of key biological importance, should be possible in principle as the number of independent diffraction intensities at a resolution better than 5 A generally exceeds the number of degrees of freedom. Here we introduce a method that adds specific information from known homologous structures but allows global and local deformations of these homology models. Our approach uses the observation that local protein structure tends to be conserved as sequence and function evolve. Cross-validation with R(free) (the free R-factor) determines the optimum deformation and influence of the homology model. For test cases at 3.5-5 A resolution with known structures at high resolution, our method gives significant improvements over conventional refinement in the model as monitored by coordinate accuracy, the definition of secondary structure and the quality of electron density maps. For re-refinements of a representative set of 19 low-resolution crystal structures from the Protein Data Bank, we find similar improvements. Thus, a structure derived from low-resolution diffraction data can have quality similar to a high-resolution structure. Our method is applicable to the study of weakly diffracting crystals using X-ray micro-diffraction as well as data from new X-ray light sources. Use of homology information is not restricted to X-ray crystallography and cryo-electron microscopy: as optical imaging advances to subnanometre resolution, it can use similar tools.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2859093/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2859093/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schroder, Gunnar F -- Levitt, Michael -- Brunger, Axel T -- EY016525/EY/NEI NIH HHS/ -- GM63718/GM/NIGMS NIH HHS/ -- R01 GM063817/GM/NIGMS NIH HHS/ -- U54 GM072970/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2010 Apr 22;464(7292):1218-22. doi: 10.1038/nature08892. Epub 2010 Apr 7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institut fur Strukturbiologie und Biophysik (ISB-3), Forschungszentrum Julich, 52425 Julich, Germany. gu.schroeder@fz-juelich.de〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20376006" target="_blank"〉PubMed〈/a〉
    Keywords: Crystallization ; Crystallography, X-Ray/*methods ; Databases, Protein ; Electrons ; Likelihood Functions ; Models, Molecular ; Oligopeptides/chemistry ; Protein Conformation ; Software ; Static Electricity
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 22
    facet.materialart.
    Unknown
    Chemistry: Breaking the billion-hertz barrier (2010)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2010-02-05
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bhattacharya, Ananyo -- England -- Nature. 2010 Feb 4;463(7281):605-6. doi: 10.1038/463605a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20130626" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Child ; Crystallization ; Crystallography, X-Ray ; Diacylglycerol Kinase/chemistry ; Humans ; Magnetic Resonance Spectroscopy/*instrumentation/*methods ; Metabolomics/instrumentation/methods ; Models, Molecular ; Protein Conformation
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 23
    facet.materialart.
    Unknown
    A conserved spider silk domain acts as a molecular switch that controls fibre assembly (2010)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2010-05-14
    Description: A huge variety of proteins are able to form fibrillar structures, especially at high protein concentrations. Hence, it is surprising that spider silk proteins can be stored in a soluble form at high concentrations and transformed into extremely stable fibres on demand. Silk proteins are reminiscent of amphiphilic block copolymers containing stretches of polyalanine and glycine-rich polar elements forming a repetitive core flanked by highly conserved non-repetitive amino-terminal and carboxy-terminal domains. The N-terminal domain comprises a secretion signal, but further functions remain unassigned. The C-terminal domain was implicated in the control of solubility and fibre formation initiated by changes in ionic composition and mechanical stimuli known to align the repetitive sequence elements and promote beta-sheet formation. However, despite recent structural data, little is known about this remarkable behaviour in molecular detail. Here we present the solution structure of the C-terminal domain of a spider dragline silk protein and provide evidence that the structural state of this domain is essential for controlled switching between the storage and assembly forms of silk proteins. In addition, the C-terminal domain also has a role in the alignment of secondary structural features formed by the repetitive elements in the backbone of spider silk proteins, which is known to be important for the mechanical properties of the fibre.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hagn, Franz -- Eisoldt, Lukas -- Hardy, John G -- Vendrely, Charlotte -- Coles, Murray -- Scheibel, Thomas -- Kessler, Horst -- England -- Nature. 2010 May 13;465(7295):239-42. doi: 10.1038/nature08936.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Integrated Protein Science (CIPSM), Technische Universitat Munchen, 85747 Garching, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20463741" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Calorimetry, Differential Scanning ; Circular Dichroism ; *Conserved Sequence ; Hydrophobic and Hydrophilic Interactions ; Magnetic Resonance Spectroscopy ; Models, Molecular ; Protein Structure, Tertiary ; Silk/*chemistry/*metabolism ; Spectrometry, Fluorescence ; Spectroscopy, Fourier Transform Infrared ; Spiders/*chemistry
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 24
    facet.materialart.
    Unknown
    Ligand-specific regulation of the extracellular surface of a G-protein-coupled receptor (2010)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2010-01-08
    Description: G-protein-coupled receptors (GPCRs) are seven-transmembrane proteins that mediate most cellular responses to hormones and neurotransmitters. They are the largest group of therapeutic targets for a broad spectrum of diseases. Recent crystal structures of GPCRs have revealed structural conservation extending from the orthosteric ligand-binding site in the transmembrane core to the cytoplasmic G-protein-coupling domains. In contrast, the extracellular surface (ECS) of GPCRs is remarkably diverse and is therefore an ideal target for the discovery of subtype-selective drugs. However, little is known about the functional role of the ECS in receptor activation, or about conformational coupling of this surface to the native ligand-binding pocket. Here we use NMR spectroscopy to investigate ligand-specific conformational changes around a central structural feature in the ECS of the beta(2) adrenergic receptor: a salt bridge linking extracellular loops 2 and 3. Small-molecule drugs that bind within the transmembrane core and exhibit different efficacies towards G-protein activation (agonist, neutral antagonist and inverse agonist) also stabilize distinct conformations of the ECS. We thereby demonstrate conformational coupling between the ECS and the orthosteric binding site, showing that drugs targeting this diverse surface could function as allosteric modulators with high subtype selectivity. Moreover, these studies provide a new insight into the dynamic behaviour of GPCRs not addressable by static, inactive-state crystal structures.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2805469/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2805469/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bokoch, Michael P -- Zou, Yaozhong -- Rasmussen, Soren G F -- Liu, Corey W -- Nygaard, Rie -- Rosenbaum, Daniel M -- Fung, Juan Jose -- Choi, Hee-Jung -- Thian, Foon Sun -- Kobilka, Tong Sun -- Puglisi, Joseph D -- Weis, William I -- Pardo, Leonardo -- Prosser, R Scott -- Mueller, Luciano -- Kobilka, Brian K -- GM56169/GM/NIGMS NIH HHS/ -- NS028471/NS/NINDS NIH HHS/ -- R01 GM056169/GM/NIGMS NIH HHS/ -- R01 GM056169-13/GM/NIGMS NIH HHS/ -- R21 MH082313/MH/NIMH NIH HHS/ -- R21 MH082313-01A1/MH/NIMH NIH HHS/ -- R37 NS028471/NS/NINDS NIH HHS/ -- R37 NS028471-19/NS/NINDS NIH HHS/ -- England -- Nature. 2010 Jan 7;463(7277):108-12. doi: 10.1038/nature08650.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, California 94305, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20054398" target="_blank"〉PubMed〈/a〉
    Keywords: Adrenergic beta-2 Receptor Agonists ; Adrenergic beta-2 Receptor Antagonists ; Allosteric Regulation/drug effects ; Binding Sites ; Crystallography, X-Ray ; Drug Inverse Agonism ; Ethanolamines/pharmacology ; Formoterol Fumarate ; Humans ; Ligands ; Lysine/analogs & derivatives/metabolism ; Methylation ; Models, Molecular ; Mutant Proteins ; Nuclear Magnetic Resonance, Biomolecular ; Propanolamines/metabolism/pharmacology ; Protein Structure, Tertiary/drug effects ; Receptors, Adrenergic, beta-2/*chemistry/*metabolism ; Static Electricity ; Substrate Specificity
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 25
    facet.materialart.
    Unknown
    Genomics goes beyond DNA sequence (2010)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2010-05-14
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Katsnelson, Alla -- England -- Nature. 2010 May 13;465(7295):145. doi: 10.1038/465145a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20463710" target="_blank"〉PubMed〈/a〉
    Keywords: *DNA Methylation ; Epigenesis, Genetic/*genetics ; Genome, Human/genetics ; Genomics/*methods ; Humans ; Models, Molecular ; Neoplasms/genetics ; Sequence Analysis, DNA/*methods
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 26
    facet.materialart.
    Unknown
    Predicting protein structures with a multiplayer online game (2010)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2010-08-06
    Description: People exert large amounts of problem-solving effort playing computer games. Simple image- and text-recognition tasks have been successfully 'crowd-sourced' through games, but it is not clear if more complex scientific problems can be solved with human-directed computing. Protein structure prediction is one such problem: locating the biologically relevant native conformation of a protein is a formidable computational challenge given the very large size of the search space. Here we describe Foldit, a multiplayer online game that engages non-scientists in solving hard prediction problems. Foldit players interact with protein structures using direct manipulation tools and user-friendly versions of algorithms from the Rosetta structure prediction methodology, while they compete and collaborate to optimize the computed energy. We show that top-ranked Foldit players excel at solving challenging structure refinement problems in which substantial backbone rearrangements are necessary to achieve the burial of hydrophobic residues. Players working collaboratively develop a rich assortment of new strategies and algorithms; unlike computational approaches, they explore not only the conformational space but also the space of possible search strategies. The integration of human visual problem-solving and strategy development capabilities with traditional computational algorithms through interactive multiplayer games is a powerful new approach to solving computationally-limited scientific problems.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2956414/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2956414/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cooper, Seth -- Khatib, Firas -- Treuille, Adrien -- Barbero, Janos -- Lee, Jeehyung -- Beenen, Michael -- Leaver-Fay, Andrew -- Baker, David -- Popovic, Zoran -- Players, Foldit -- Howard Hughes Medical Institute/ -- England -- Nature. 2010 Aug 5;466(7307):756-60. doi: 10.1038/nature09304.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Computer Science and Engineering, University of Washington, Box 352350, Seattle, Washington 98195, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20686574" target="_blank"〉PubMed〈/a〉
    Keywords: Algorithms ; Computational Biology/*methods ; Computer Graphics ; Computer Simulation ; Cooperative Behavior ; Cues ; *Games, Experimental ; *Group Processes ; Humans ; Hydrogen Bonding ; Hydrophobic and Hydrophilic Interactions ; Imaging, Three-Dimensional ; *Internet ; Leisure Activities ; Models, Molecular ; Nuclear Magnetic Resonance, Biomolecular ; Photic Stimulation ; *Problem Solving ; Protein Conformation ; *Protein Folding ; Proteins/*chemistry/metabolism ; Stochastic Processes ; Thermodynamics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 27
    facet.materialart.
    Unknown
    Crystal structure of the human symplekin-Ssu72-CTD phosphopeptide complex (2010)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2010-09-24
    Description: Symplekin (Pta1 in yeast) is a scaffold in the large protein complex that is required for 3'-end cleavage and polyadenylation of eukaryotic messenger RNA precursors (pre-mRNAs); it also participates in transcription initiation and termination by RNA polymerase II (Pol II). Symplekin mediates interactions between many different proteins in this machinery, although the molecular basis for its function is not known. Here we report the crystal structure at 2.4 A resolution of the amino-terminal domain (residues 30-340) of human symplekin in a ternary complex with the Pol II carboxy-terminal domain (CTD) Ser 5 phosphatase Ssu72 (refs 7, 10-17) and a CTD Ser 5 phosphopeptide. The N-terminal domain of symplekin has the ARM or HEAT fold, with seven pairs of antiparallel alpha-helices arranged in the shape of an arc. The structure of Ssu72 has some similarity to that of low-molecular-mass phosphotyrosine protein phosphatase, although Ssu72 has a unique active-site landscape as well as extra structural features at the C terminus that are important for interaction with symplekin. Ssu72 is bound to the concave face of symplekin, and engineered mutations in this interface can abolish interactions between the two proteins. The CTD peptide is bound in the active site of Ssu72, with the pSer 5-Pro 6 peptide bond in the cis configuration, which contrasts with all other known CTD peptide conformations. Although the active site of Ssu72 is about 25 A from the interface with symplekin, we found that the symplekin N-terminal domain stimulates Ssu72 CTD phosphatase activity in vitro. Furthermore, the N-terminal domain of symplekin inhibits polyadenylation in vitro, but only when coupled to transcription. Because catalytically active Ssu72 overcomes this inhibition, our results show a role for mammalian Ssu72 in transcription-coupled pre-mRNA 3'-end processing.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3038789/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3038789/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Xiang, Kehui -- Nagaike, Takashi -- Xiang, Song -- Kilic, Turgay -- Beh, Maia M -- Manley, James L -- Tong, Liang -- GM028983/GM/NIGMS NIH HHS/ -- GM077175/GM/NIGMS NIH HHS/ -- P30 EB009998/EB/NIBIB NIH HHS/ -- R01 GM028983/GM/NIGMS NIH HHS/ -- R01 GM028983-31/GM/NIGMS NIH HHS/ -- R01 GM077175/GM/NIGMS NIH HHS/ -- R01 GM077175-04/GM/NIGMS NIH HHS/ -- England -- Nature. 2010 Oct 7;467(7316):729-33. doi: 10.1038/nature09391. Epub 2010 Sep 22.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biological Sciences, Columbia University, New York, New York 10027, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20861839" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Binding Sites ; Carrier Proteins/*chemistry/genetics/*metabolism ; Catalytic Domain ; Crystallography, X-Ray ; Drosophila Proteins/chemistry ; Humans ; Models, Molecular ; Nuclear Proteins/*chemistry/genetics/*metabolism ; Phosphopeptides/chemistry/*metabolism ; Phosphoprotein Phosphatases/chemistry/genetics/metabolism ; Polyadenylation ; Protein Binding ; Protein Structure, Secondary ; Protein Structure, Tertiary ; RNA Polymerase II/*chemistry/*metabolism ; Saccharomyces cerevisiae Proteins/chemistry ; Substrate Specificity ; mRNA Cleavage and Polyadenylation Factors/chemistry
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 28
    facet.materialart.
    Unknown
    The structural basis for membrane binding and pore formation by lymphocyte perforin (2010)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2010-11-03
    Description: Natural killer cells and cytotoxic T lymphocytes accomplish the critically important function of killing virus-infected and neoplastic cells. They do this by releasing the pore-forming protein perforin and granzyme proteases from cytoplasmic granules into the cleft formed between the abutting killer and target cell membranes. Perforin, a 67-kilodalton multidomain protein, oligomerizes to form pores that deliver the pro-apoptopic granzymes into the cytosol of the target cell. The importance of perforin is highlighted by the fatal consequences of congenital perforin deficiency, with more than 50 different perforin mutations linked to familial haemophagocytic lymphohistiocytosis (type 2 FHL). Here we elucidate the mechanism of perforin pore formation by determining the X-ray crystal structure of monomeric murine perforin, together with a cryo-electron microscopy reconstruction of the entire perforin pore. Perforin is a thin 'key-shaped' molecule, comprising an amino-terminal membrane attack complex perforin-like (MACPF)/cholesterol dependent cytolysin (CDC) domain followed by an epidermal growth factor (EGF) domain that, together with the extreme carboxy-terminal sequence, forms a central shelf-like structure. A C-terminal C2 domain mediates initial, Ca(2+)-dependent membrane binding. Most unexpectedly, however, electron microscopy reveals that the orientation of the perforin MACPF domain in the pore is inside-out relative to the subunit arrangement in CDCs. These data reveal remarkable flexibility in the mechanism of action of the conserved MACPF/CDC fold and provide new insights into how related immune defence molecules such as complement proteins assemble into pores.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Law, Ruby H P -- Lukoyanova, Natalya -- Voskoboinik, Ilia -- Caradoc-Davies, Tom T -- Baran, Katherine -- Dunstone, Michelle A -- D'Angelo, Michael E -- Orlova, Elena V -- Coulibaly, Fasseli -- Verschoor, Sandra -- Browne, Kylie A -- Ciccone, Annette -- Kuiper, Michael J -- Bird, Phillip I -- Trapani, Joseph A -- Saibil, Helen R -- Whisstock, James C -- 079605/Wellcome Trust/United Kingdom -- BB/D008573/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- Arthritis Research UK/United Kingdom -- Biotechnology and Biological Sciences Research Council/United Kingdom -- Wellcome Trust/United Kingdom -- England -- Nature. 2010 Nov 18;468(7322):447-51. doi: 10.1038/nature09518. Epub 2010 Oct 31.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Molecular Biology, Monash University, Clayton, Melbourne, Victoria 3800, Australia.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21037563" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Membrane/*metabolism ; Cholesterol/metabolism ; Cryoelectron Microscopy ; Crystallography, X-Ray ; Epidermal Growth Factor/chemistry ; Granzymes/metabolism ; Humans ; Lymphocytes/*metabolism ; Mice ; Models, Molecular ; Pore Forming Cytotoxic Proteins/*chemistry/genetics/*metabolism/ultrastructure ; Protein Structure, Tertiary
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 29
    facet.materialart.
    Unknown
    Structure of a cation-bound multidrug and toxic compound extrusion transporter (2010)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2010-09-24
    Description: Transporter proteins from the MATE (multidrug and toxic compound extrusion) family are vital in metabolite transport in plants, directly affecting crop yields worldwide. MATE transporters also mediate multiple-drug resistance (MDR) in bacteria and mammals, modulating the efficacy of many pharmaceutical drugs used in the treatment of a variety of diseases. MATE transporters couple substrate transport to electrochemical gradients and are the only remaining class of MDR transporters whose structure has not been determined. Here we report the X-ray structure of the MATE transporter NorM from Vibrio cholerae determined to 3.65 A, revealing an outward-facing conformation with two portals open to the outer leaflet of the membrane and a unique topology of the predicted 12 transmembrane helices distinct from any other known MDR transporter. We also report a cation-binding site in close proximity to residues previously deemed critical for transport. This conformation probably represents a stage of the transport cycle with high affinity for monovalent cations and low affinity for substrates.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3152480/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3152480/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉He, Xiao -- Szewczyk, Paul -- Karyakin, Andrey -- Evin, Mariah -- Hong, Wen-Xu -- Zhang, Qinghai -- Chang, Geoffrey -- GM70480/GM/NIGMS NIH HHS/ -- GM73197/GM/NIGMS NIH HHS/ -- P50 GM073197/GM/NIGMS NIH HHS/ -- P50 GM073197-07/GM/NIGMS NIH HHS/ -- R01 GM070480/GM/NIGMS NIH HHS/ -- R01 GM070480-01A1/GM/NIGMS NIH HHS/ -- R01 GM070480-02/GM/NIGMS NIH HHS/ -- R01 GM070480-03/GM/NIGMS NIH HHS/ -- R01 GM070480-04/GM/NIGMS NIH HHS/ -- England -- Nature. 2010 Oct 21;467(7318):991-4. doi: 10.1038/nature09408. Epub 2010 Sep 22.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, CB105, La Jolla, California 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20861838" target="_blank"〉PubMed〈/a〉
    Keywords: Antiporters/*chemistry/genetics/*metabolism ; Bacterial Proteins/*chemistry/genetics/*metabolism ; Binding Sites ; Cations/chemistry/metabolism ; Crystallography, X-Ray ; Cysteine/genetics/metabolism ; Ion Transport ; Models, Molecular ; Protein Conformation ; Reproducibility of Results ; Static Electricity ; Substrate Specificity ; Vibrio cholerae/*chemistry
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 30
    facet.materialart.
    Unknown
    An unprecedented nucleic acid capture mechanism for excision of DNA damage (2010)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2010-10-12
    Description: DNA glycosylases that remove alkylated and deaminated purine nucleobases are essential DNA repair enzymes that protect the genome, and at the same time confound cancer alkylation therapy, by excising cytotoxic N3-methyladenine bases formed by DNA-targeting anticancer compounds. The basis for glycosylase specificity towards N3- and N7-alkylpurines is believed to result from intrinsic instability of the modified bases and not from direct enzyme functional group chemistry. Here we present crystal structures of the recently discovered Bacillus cereus AlkD glycosylase in complex with DNAs containing alkylated, mismatched and abasic nucleotides. Unlike other glycosylases, AlkD captures the extrahelical lesion in a solvent-exposed orientation, providing an illustration for how hydrolysis of N3- and N7-alkylated bases may be facilitated by increased lifetime out of the DNA helix. The structures and supporting biochemical analysis of base flipping and catalysis reveal how the HEAT repeats of AlkD distort the DNA backbone to detect non-Watson-Crick base pairs without duplex intercalation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4160814/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4160814/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rubinson, Emily H -- Gowda, A S Prakasha -- Spratt, Thomas E -- Gold, Barry -- Eichman, Brandt F -- P30 CA068485/CA/NCI NIH HHS/ -- P30 ES000267/ES/NIEHS NIH HHS/ -- R01 CA029088/CA/NCI NIH HHS/ -- R01 CA29088/CA/NCI NIH HHS/ -- T32 ES007028/ES/NIEHS NIH HHS/ -- England -- Nature. 2010 Nov 18;468(7322):406-11. doi: 10.1038/nature09428. Epub 2010 Oct 3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biological Sciences and Center for Structural Biology, Vanderbilt University, Nashville, Tennessee 37232, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20927102" target="_blank"〉PubMed〈/a〉
    Keywords: Alkylation ; Bacillus cereus/*enzymology ; Base Sequence ; Biocatalysis ; Crystallography, X-Ray ; DNA/chemistry/genetics/*metabolism ; *DNA Damage ; DNA Glycosylases/*metabolism ; DNA Repair/*physiology ; Hydrolysis ; Models, Molecular ; Nucleic Acid Conformation ; Protein Binding ; Solvents/chemistry ; Thermodynamics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 31
    facet.materialart.
    Unknown
    Structure of the amantadine binding site of influenza M2 proton channels in lipid bilayers (2010)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2010-02-05
    Description: The M2 protein of influenza A virus is a membrane-spanning tetrameric proton channel targeted by the antiviral drugs amantadine and rimantadine. Resistance to these drugs has compromised their effectiveness against many influenza strains, including pandemic H1N1. A recent crystal structure of M2(22-46) showed electron densities attributed to a single amantadine in the amino-terminal half of the pore, indicating a physical occlusion mechanism for inhibition. However, a solution NMR structure of M2(18-60) showed four rimantadines bound to the carboxy-terminal lipid-facing surface of the helices, suggesting an allosteric mechanism. Here we show by solid-state NMR spectroscopy that two amantadine-binding sites exist in M2 in phospholipid bilayers. The high-affinity site, occupied by a single amantadine, is located in the N-terminal channel lumen, surrounded by residues mutated in amantadine-resistant viruses. Quantification of the protein-amantadine distances resulted in a 0.3 A-resolution structure of the high-affinity binding site. The second, low-affinity, site was observed on the C-terminal protein surface, but only when the drug reaches high concentrations in the bilayer. The orientation and dynamics of the drug are distinct in the two sites, as shown by (2)H NMR. These results indicate that amantadine physically occludes the M2 channel, thus paving the way for developing new antiviral drugs against influenza viruses. The study demonstrates the ability of solid-state NMR to elucidate small-molecule interactions with membrane proteins and determine high-resolution structures of their complexes.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2818718/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2818718/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cady, Sarah D -- Schmidt-Rohr, Klaus -- Wang, Jun -- Soto, Cinque S -- Degrado, William F -- Hong, Mei -- AI74571/AI/NIAID NIH HHS/ -- GM088204/GM/NIGMS NIH HHS/ -- GM56423/GM/NIGMS NIH HHS/ -- R01 GM056423/GM/NIGMS NIH HHS/ -- R01 GM056423-12/GM/NIGMS NIH HHS/ -- R01 GM088204/GM/NIGMS NIH HHS/ -- R01 GM088204-01/GM/NIGMS NIH HHS/ -- U01 AI074571/AI/NIAID NIH HHS/ -- U01 AI074571-02/AI/NIAID NIH HHS/ -- England -- Nature. 2010 Feb 4;463(7281):689-92. doi: 10.1038/nature08722.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry, Iowa State University, Ames, Iowa 50011 2, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20130653" target="_blank"〉PubMed〈/a〉
    Keywords: Amantadine/chemistry/*metabolism/pharmacology ; Amino Acid Sequence ; Antiviral Agents/chemistry/*metabolism/pharmacology ; Binding Sites ; Crystallography, X-Ray ; Dimyristoylphosphatidylcholine/chemistry/metabolism ; Hydrogen-Ion Concentration ; Influenza A virus/*chemistry/drug effects ; Lipid Bilayers/chemistry/*metabolism ; Models, Molecular ; Molecular Sequence Data ; Nuclear Magnetic Resonance, Biomolecular ; Protein Conformation ; Structure-Activity Relationship ; Temperature ; Viral Matrix Proteins/antagonists & inhibitors/*chemistry/*metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 32
    facet.materialart.
    Unknown
    The architecture of respiratory complex I (2010)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2010-05-28
    Description: Complex I is the first enzyme of the respiratory chain and has a central role in cellular energy production, coupling electron transfer between NADH and quinone to proton translocation by an unknown mechanism. Dysfunction of complex I has been implicated in many human neurodegenerative diseases. We have determined the structure of its hydrophilic domain previously. Here, we report the alpha-helical structure of the membrane domain of complex I from Escherichia coli at 3.9 A resolution. The antiporter-like subunits NuoL/M/N each contain 14 conserved transmembrane (TM) helices. Two of them are discontinuous, as in some transporters. Unexpectedly, subunit NuoL also contains a 110-A long amphipathic alpha-helix, spanning almost the entire length of the domain. Furthermore, we have determined the structure of the entire complex I from Thermus thermophilus at 4.5 A resolution. The L-shaped assembly consists of the alpha-helical model for the membrane domain, with 63 TM helices, and the known structure of the hydrophilic domain. The architecture of the complex provides strong clues about the coupling mechanism: the conformational changes at the interface of the two main domains may drive the long amphipathic alpha-helix of NuoL in a piston-like motion, tilting nearby discontinuous TM helices, resulting in proton translocation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Efremov, Rouslan G -- Baradaran, Rozbeh -- Sazanov, Leonid A -- MC_U105674180/Medical Research Council/United Kingdom -- Medical Research Council/United Kingdom -- England -- Nature. 2010 May 27;465(7297):441-5. doi: 10.1038/nature09066.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Medical Research Council Mitochondrial Biology Unit, Wellcome Trust/MRC Building, Hills Road, Cambridge CB2 0XY, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20505720" target="_blank"〉PubMed〈/a〉
    Keywords: Benzoquinones/metabolism ; Binding Sites ; Cell Membrane/metabolism ; Crystallography, X-Ray ; Electron Transport Complex I/*chemistry/*metabolism ; Escherichia coli/*enzymology ; Models, Molecular ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Protein Subunits/*chemistry/*metabolism ; Structure-Activity Relationship ; Thermus thermophilus/*enzymology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 33
    facet.materialart.
    Unknown
    Transfer of carbohydrate-active enzymes from marine bacteria to Japanese gut microbiota (2010)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2010-04-09
    Description: Gut microbes supply the human body with energy from dietary polysaccharides through carbohydrate active enzymes, or CAZymes, which are absent in the human genome. These enzymes target polysaccharides from terrestrial plants that dominated diet throughout human evolution. The array of CAZymes in gut microbes is highly diverse, exemplified by the human gut symbiont Bacteroides thetaiotaomicron, which contains 261 glycoside hydrolases and polysaccharide lyases, as well as 208 homologues of susC and susD-genes coding for two outer membrane proteins involved in starch utilization. A fundamental question that, to our knowledge, has yet to be addressed is how this diversity evolved by acquiring new genes from microbes living outside the gut. Here we characterize the first porphyranases from a member of the marine Bacteroidetes, Zobellia galactanivorans, active on the sulphated polysaccharide porphyran from marine red algae of the genus Porphyra. Furthermore, we show that genes coding for these porphyranases, agarases and associated proteins have been transferred to the gut bacterium Bacteroides plebeius isolated from Japanese individuals. Our comparative gut metagenome analyses show that porphyranases and agarases are frequent in the Japanese population and that they are absent in metagenome data from North American individuals. Seaweeds make an important contribution to the daily diet in Japan (14.2 g per person per day), and Porphyra spp. (nori) is the most important nutritional seaweed, traditionally used to prepare sushi. This indicates that seaweeds with associated marine bacteria may have been the route by which these novel CAZymes were acquired in human gut bacteria, and that contact with non-sterile food may be a general factor in CAZyme diversity in human gut microbes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hehemann, Jan-Hendrik -- Correc, Gaelle -- Barbeyron, Tristan -- Helbert, William -- Czjzek, Mirjam -- Michel, Gurvan -- England -- Nature. 2010 Apr 8;464(7290):908-12. doi: 10.1038/nature08937.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Universite Pierre et Marie Curie, Paris, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20376150" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptation, Physiological/physiology ; Bacteroides/*enzymology/genetics ; Biological Evolution ; Crystallography, X-Ray ; Cultural Diversity ; Diet ; Eukaryota/chemistry/metabolism ; Feces/enzymology/microbiology ; *Food Microbiology ; Gene Transfer, Horizontal ; Genome, Bacterial/genetics ; Glycoside Hydrolases/chemistry/isolation & purification/*metabolism ; Humans ; Intestines/*microbiology ; Japan ; *Marine Biology ; *Metagenome ; Models, Molecular ; North America ; Phylogeny ; Porphyra/chemistry/metabolism/microbiology ; Protein Conformation ; Sepharose/*analogs & derivatives/chemistry/metabolism ; Substrate Specificity
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 34
    facet.materialart.
    Unknown
    The proteasome antechamber maintains substrates in an unfolded state (2010)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2010-10-15
    Description: Eukaryotes and archaea use a protease called the proteasome that has an integral role in maintaining cellular function through the selective degradation of proteins. Proteolysis occurs in a barrel-shaped 20S core particle, which in Thermoplasma acidophilum is built from four stacked homoheptameric rings of subunits, alpha and beta, arranged alpha(7)beta(7)beta(7)alpha(7) (ref. 5). These rings form three interconnected cavities, including a pair of antechambers (formed by alpha(7)beta(7)) through which substrates are passed before degradation and a catalytic chamber (beta(7)beta(7)) where the peptide-bond hydrolysis reaction occurs. Although it is clear that substrates must be unfolded to enter through narrow, gated passageways (13 A in diameter) located on the alpha-rings, the structural and dynamical properties of substrates inside the proteasome antechamber remain unclear. Confinement in the antechamber might be expected to promote folding and thus impede proteolysis. Here we investigate the folding, stability and dynamics of three small protein substrates in the antechamber by methyl transverse-relaxation-optimized NMR spectroscopy. We show that these substrates interact actively with the antechamber walls and have drastically altered kinetic and equilibrium properties that maintain them in unstructured states so as to be accessible for hydrolysis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ruschak, Amy M -- Religa, Tomasz L -- Breuer, Sarah -- Witt, Susanne -- Kay, Lewis E -- Canadian Institutes of Health Research/Canada -- England -- Nature. 2010 Oct 14;467(7317):868-71. doi: 10.1038/nature09444.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Departments of Molecular Genetics, Biochemistry and Chemistry, The University of Toronto, Toronto, Ontario M5S 1A8, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20944750" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Hydrolysis ; Kinetics ; Magnetic Resonance Spectroscopy ; Models, Molecular ; Molecular Sequence Data ; Proteasome Endopeptidase Complex/*chemistry/*metabolism ; Protein Folding ; *Protein Processing, Post-Translational ; Protein Stability ; Protein Subunits/chemistry/metabolism ; *Protein Unfolding ; Thermodynamics ; Thermoplasma/enzymology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 35
    facet.materialart.
    Unknown
    Atomically precise bottom-up fabrication of graphene nanoribbons (2010)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2010-07-24
    Description: Graphene nanoribbons-narrow and straight-edged stripes of graphene, or single-layer graphite-are predicted to exhibit electronic properties that make them attractive for the fabrication of nanoscale electronic devices. In particular, although the two-dimensional parent material graphene exhibits semimetallic behaviour, quantum confinement and edge effects should render all graphene nanoribbons with widths smaller than 10 nm semiconducting. But exploring the potential of graphene nanoribbons is hampered by their limited availability: although they have been made using chemical, sonochemical and lithographic methods as well as through the unzipping of carbon nanotubes, the reliable production of graphene nanoribbons smaller than 10 nm with chemical precision remains a significant challenge. Here we report a simple method for the production of atomically precise graphene nanoribbons of different topologies and widths, which uses surface-assisted coupling of molecular precursors into linear polyphenylenes and their subsequent cyclodehydrogenation. The topology, width and edge periphery of the graphene nanoribbon products are defined by the structure of the precursor monomers, which can be designed to give access to a wide range of different graphene nanoribbons. We expect that our bottom-up approach to the atomically precise fabrication of graphene nanoribbons will finally enable detailed experimental investigations of the properties of this exciting class of materials. It should even provide a route to graphene nanoribbon structures with engineered chemical and electronic properties, including the theoretically predicted intraribbon quantum dots, superlattice structures and magnetic devices based on specific graphene nanoribbon edge states.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cai, Jinming -- Ruffieux, Pascal -- Jaafar, Rached -- Bieri, Marco -- Braun, Thomas -- Blankenburg, Stephan -- Muoth, Matthias -- Seitsonen, Ari P -- Saleh, Moussa -- Feng, Xinliang -- Mullen, Klaus -- Fasel, Roman -- England -- Nature. 2010 Jul 22;466(7305):470-3. doi: 10.1038/nature09211.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Empa, Swiss Federal Laboratories for Materials Science and Technology, Thun and 8600 Dubendorf, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20651687" target="_blank"〉PubMed〈/a〉
    Keywords: Electronics/*instrumentation ; Graphite/*chemistry ; Hydrogenation ; Models, Molecular ; Molecular Conformation ; Nanotubes, Carbon/*chemistry
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 36
    facet.materialart.
    Unknown
    Principles of stop-codon reading on the ribosome (2010)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2010-06-01
    Description: In termination of protein synthesis, the bacterial release factors RF1 and RF2 bind to the ribosome through specific recognition of messenger RNA stop codons and trigger hydrolysis of the bond between the nascent polypeptide and the transfer RNA at the peptidyl-tRNA site, thereby releasing the newly synthesized protein. The release factors are highly specific for a U in the first stop-codon position and recognize different combinations of purines in the second and third positions, with RF1 reading UAA and UAG and RF2 reading UAA and UGA. With recently determined crystal structures of termination complexes, it has become possible to decipher the energetics of stop-codon reading by computational analysis and to clarify the origin of the high release-factor binding accuracy. Here we report molecular dynamics free-energy calculations on different cognate and non-cognate termination complexes. The simulations quantitatively explain the basic principles of decoding in all three codon positions and reveal the key elements responsible for specificity of the release factors. The overall reading mechanism involves hitherto unidentified interactions and recognition switches that cannot be described in terms of a tripeptide anticodon model. Further simulations of complexes with tRNA(Trp), the tRNA recognizing the triplet codon for Trp, explain the observation of a 'leaky' stop codon and highlight the fundamentally different third position reading by RF2, which leads to a high stop-codon specificity with strong discrimination against the Trp codon. The simulations clearly illustrate the versatility of codon reading by protein, which goes far beyond tRNA mimicry.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sund, Johan -- Ander, Martin -- Aqvist, Johan -- England -- Nature. 2010 Jun 17;465(7300):947-50. doi: 10.1038/nature09082. Epub 2010 May 30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cell and Molecular Biology, Uppsala University, Biomedical Center, Box 596, SE-751 24 Uppsala, Sweden.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20512119" target="_blank"〉PubMed〈/a〉
    Keywords: Bacteria/chemistry/genetics/*metabolism ; Codon, Terminator/*chemistry/genetics/*metabolism ; Models, Molecular ; Molecular Dynamics Simulation ; Peptide Termination Factors/chemistry/genetics/*metabolism ; Protein Binding/genetics ; Protein Structure, Tertiary ; RNA, Transfer/metabolism ; Ribosomes/genetics/*metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 37
    facet.materialart.
    Unknown
    Iron-catalysed oxidation intermediates captured in a DNA repair dioxygenase (2010)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2010-11-12
    Description: Mononuclear iron-containing oxygenases conduct a diverse variety of oxidation functions in biology, including the oxidative demethylation of methylated nucleic acids and histones. Escherichia coli AlkB is the first such enzyme that was discovered to repair methylated nucleic acids, which are otherwise cytotoxic and/or mutagenic. AlkB human homologues are known to play pivotal roles in various processes. Here we present structural characterization of oxidation intermediates for these demethylases. Using a chemical cross-linking strategy, complexes of AlkB-double stranded DNA (dsDNA) containing 1,N(6)-etheno adenine (epsilonA), N(3)-methyl thymine (3-meT) and N(3)-methyl cytosine (3-meC) are stabilized and crystallized, respectively. Exposing these crystals, grown under anaerobic conditions containing iron(II) and alpha-ketoglutarate (alphaKG), to dioxygen initiates oxidation in crystallo. Glycol (from epsilonA) and hemiaminal (from 3-meT) intermediates are captured; a zwitterionic intermediate (from 3-meC) is also proposed, based on crystallographic observations and computational analysis. The observation of these unprecedented intermediates provides direct support for the oxidative demethylation mechanism for these demethylases. This study also depicts a general mechanistic view of how a methyl group is oxidatively removed from different biological substrates.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3058853/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3058853/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yi, Chengqi -- Jia, Guifang -- Hou, Guanhua -- Dai, Qing -- Zhang, Wen -- Zheng, Guanqun -- Jian, Xing -- Yang, Cai-Guang -- Cui, Qiang -- He, Chuan -- GM071440/GM/NIGMS NIH HHS/ -- GM084028/GM/NIGMS NIH HHS/ -- R01 GM071440/GM/NIGMS NIH HHS/ -- R01 GM071440-06/GM/NIGMS NIH HHS/ -- England -- Nature. 2010 Nov 11;468(7321):330-3. doi: 10.1038/nature09497.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry and Institute for Biophysical Dynamics, The University of Chicago, 929 East 57th Street, Chicago, Illinois 60637, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21068844" target="_blank"〉PubMed〈/a〉
    Keywords: Catalysis ; Cross-Linking Reagents/chemistry ; Crystallization ; Crystallography, X-Ray ; DNA/chemistry/metabolism ; *DNA Repair ; DNA Repair Enzymes/metabolism ; Dioxygenases/chemistry/*metabolism ; Escherichia coli/*enzymology ; Escherichia coli Proteins/chemistry/*metabolism ; Humans ; Iron/*metabolism ; Ketoglutaric Acids/metabolism ; Methylation ; Mixed Function Oxygenases/chemistry/*metabolism ; Models, Molecular ; Oxidation-Reduction ; Static Electricity ; Substrate Specificity
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 38
    facet.materialart.
    Unknown
    Tracking G-protein-coupled receptor activation using genetically encoded infrared probes (2010)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2010-04-13
    Description: Rhodopsin is a prototypical heptahelical family A G-protein-coupled receptor (GPCR) responsible for dim-light vision. Light isomerizes rhodopsin's retinal chromophore and triggers concerted movements of transmembrane helices, including an outward tilting of helix 6 (H6) and a smaller movement of H5, to create a site for G-protein binding and activation. However, the precise temporal sequence and mechanism underlying these helix rearrangements is unclear. We used site-directed non-natural amino acid mutagenesis to engineer rhodopsin with p-azido-l-phenylalanine residues incorporated at selected sites, and monitored the azido vibrational signatures using infrared spectroscopy as rhodopsin proceeded along its activation pathway. Here we report significant changes in electrostatic environments of the azido probes even in the inactive photoproduct Meta I, well before the active receptor state was formed. These early changes suggest a significant rotation of H6 and movement of the cytoplasmic part of H5 away from H3. Subsequently, a large outward tilt of H6 leads to opening of the cytoplasmic surface to form the active receptor photoproduct Meta II. Thus, our results reveal early conformational changes that precede larger rigid-body helix movements, and provide a basis to interpret recent GPCR crystal structures and to understand conformational sub-states observed during the activation of other GPCRs.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ye, Shixin -- Zaitseva, Ekaterina -- Caltabiano, Gianluigi -- Schertler, Gebhard F X -- Sakmar, Thomas P -- Deupi, Xavier -- Vogel, Reiner -- England -- Nature. 2010 Apr 29;464(7293):1386-9. doi: 10.1038/nature08948. Epub 2010 Apr 11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Molecular Biology and Biochemistry, The Rockefeller University, 1230 York Avenue, New York, New York 10065, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20383122" target="_blank"〉PubMed〈/a〉
    Keywords: Azides/analysis/*metabolism/radiation effects ; Cell Line ; Humans ; *Infrared Rays ; Models, Molecular ; Movement ; Phenylalanine/*analogs & derivatives/analysis/genetics/metabolism/radiation ; effects ; Protein Conformation ; Rhodopsin/chemistry/*genetics/*metabolism ; Spectroscopy, Fourier Transform Infrared ; Static Electricity ; Vibration
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 39
    facet.materialart.
    Unknown
    The Ndc80 kinetochore complex forms oligomeric arrays along microtubules (2010)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2010-10-15
    Description: The Ndc80 complex is a key site of regulated kinetochore-microtubule attachment (a process required for cell division), but the molecular mechanism underlying its function remains unknown. Here we present a subnanometre-resolution cryo-electron microscopy reconstruction of the human Ndc80 complex bound to microtubules, sufficient for precise docking of crystal structures of the component proteins. We find that the Ndc80 complex binds the microtubule with a tubulin monomer repeat, recognizing alpha- and beta-tubulin at both intra- and inter-tubulin dimer interfaces in a manner that is sensitive to tubulin conformation. Furthermore, Ndc80 complexes self-associate along protofilaments through interactions mediated by the amino-terminal tail of the NDC80 protein, which is the site of phospho-regulation by Aurora B kinase. The complex's mode of interaction with the microtubule and its oligomerization suggest a mechanism by which Aurora B could regulate the stability of load-bearing kinetochore-microtubule attachments.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2957311/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2957311/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Alushin, Gregory M -- Ramey, Vincent H -- Pasqualato, Sebastiano -- Ball, David A -- Grigorieff, Nikolaus -- Musacchio, Andrea -- Nogales, Eva -- Howard Hughes Medical Institute/ -- England -- Nature. 2010 Oct 14;467(7317):805-10. doi: 10.1038/nature09423.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Biophysics Graduate Group, University of California, Berkeley, California 94720, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20944740" target="_blank"〉PubMed〈/a〉
    Keywords: Binding Sites ; Cryoelectron Microscopy ; Humans ; Kinetochores/*chemistry/ultrastructure ; Microtubules/chemistry/*metabolism/ultrastructure ; Mitosis ; Models, Biological ; Models, Molecular ; Nuclear Proteins/*chemistry/*metabolism/ultrastructure ; Protein Conformation ; Tubulin/chemistry/metabolism/ultrastructure
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 40
    facet.materialart.
    Unknown
    Sphingosine-1-phosphate is a missing cofactor for the E3 ubiquitin ligase TRAF2 (2010)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2010-06-26
    Description: Tumour-necrosis factor (TNF) receptor-associated factor 2 (TRAF2) is a key component in NF-kappaB signalling triggered by TNF-alpha. Genetic evidence indicates that TRAF2 is necessary for the polyubiquitination of receptor interacting protein 1 (RIP1) that then serves as a platform for recruitment and stimulation of IkappaB kinase, leading to activation of the transcription factor NF-kappaB. Although TRAF2 is a RING domain ubiquitin ligase, direct evidence that TRAF2 catalyses the ubiquitination of RIP1 is lacking. TRAF2 binds to sphingosine kinase 1 (SphK1), one of the isoenzymes that generates the pro-survival lipid mediator sphingosine-1-phosphate (S1P) inside cells. Here we show that SphK1 and the production of S1P is necessary for lysine-63-linked polyubiquitination of RIP1, phosphorylation of IkappaB kinase and IkappaBalpha, and IkappaBalpha degradation, leading to NF-kappaB activation. These responses were mediated by intracellular S1P independently of its cell surface G-protein-coupled receptors. S1P specifically binds to TRAF2 at the amino-terminal RING domain and stimulates its E3 ligase activity. S1P, but not dihydro-S1P, markedly increased recombinant TRAF2-catalysed lysine-63-linked, but not lysine-48-linked, polyubiquitination of RIP1 in vitro in the presence of the ubiquitin conjugating enzymes (E2) UbcH13 or UbcH5a. Our data show that TRAF2 is a novel intracellular target of S1P, and that S1P is the missing cofactor for TRAF2 E3 ubiquitin ligase activity, indicating a new paradigm for the regulation of lysine-63-linked polyubiquitination. These results also highlight the key role of SphK1 and its product S1P in TNF-alpha signalling and the canonical NF-kappaB activation pathway important in inflammatory, antiapoptotic and immune processes.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2946785/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2946785/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Alvarez, Sergio E -- Harikumar, Kuzhuvelil B -- Hait, Nitai C -- Allegood, Jeremy -- Strub, Graham M -- Kim, Eugene Y -- Maceyka, Michael -- Jiang, Hualiang -- Luo, Cheng -- Kordula, Tomasz -- Milstien, Sheldon -- Spiegel, Sarah -- R01 AI050094/AI/NIAID NIH HHS/ -- R01 AI050094-09/AI/NIAID NIH HHS/ -- R01 CA061774/CA/NCI NIH HHS/ -- R01 CA061774-15/CA/NCI NIH HHS/ -- R01 CA061774-16/CA/NCI NIH HHS/ -- R01AI50094/AI/NIAID NIH HHS/ -- R01CA61774/CA/NCI NIH HHS/ -- R37 GM043880/GM/NIGMS NIH HHS/ -- R37 GM043880-18/GM/NIGMS NIH HHS/ -- R37 GM043880-19/GM/NIGMS NIH HHS/ -- R37 GM043880-20/GM/NIGMS NIH HHS/ -- R37 GM043880-21/GM/NIGMS NIH HHS/ -- R37GM043880/GM/NIGMS NIH HHS/ -- U19 AI077435/AI/NIAID NIH HHS/ -- U19 AI077435-020004/AI/NIAID NIH HHS/ -- U19 AI077435-02S10004/AI/NIAID NIH HHS/ -- U19 AI077435-030004/AI/NIAID NIH HHS/ -- U19AI077435/AI/NIAID NIH HHS/ -- England -- Nature. 2010 Jun 24;465(7301):1084-8. doi: 10.1038/nature09128.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Molecular Biology and the Massey Cancer Center, Virginia Commonwealth University School of Medicine, 1101 E. Marshall Street, Richmond, Virginia 23298, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20577214" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biocatalysis ; Cell Line ; Enzyme Activation ; Humans ; I-kappa B Kinase/metabolism ; I-kappa B Proteins/metabolism ; Lysine/metabolism ; Lysophospholipids/biosynthesis/chemistry/*metabolism ; Mice ; Models, Molecular ; NF-kappa B/metabolism ; Phosphorylation ; Phosphotransferases (Alcohol Group Acceptor)/genetics/metabolism ; Protein Binding ; Protein Structure, Tertiary ; Receptor-Interacting Protein Serine-Threonine Kinases/metabolism ; Sphingosine/*analogs & derivatives/biosynthesis/chemistry/metabolism ; Substrate Specificity ; TNF Receptor-Associated Factor 2/chemistry/*metabolism ; Tumor Necrosis Factor-alpha/pharmacology ; Ubiquitin-Conjugating Enzymes/metabolism ; Ubiquitin-Protein Ligases/*metabolism ; Ubiquitination/drug effects
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 41
    facet.materialart.
    Unknown
    Crystal structure of bacterial RNA polymerase bound with a transcription inhibitor protein (2010)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2010-12-03
    Description: The multi-subunit DNA-dependent RNA polymerase (RNAP) is the principal enzyme of transcription for gene expression. Transcription is regulated by various transcription factors. Gre factor homologue 1 (Gfh1), found in the Thermus genus, is a close homologue of the well-conserved bacterial transcription factor GreA, and inhibits transcription initiation and elongation by binding directly to RNAP. The structural basis of transcription inhibition by Gfh1 has remained elusive, although the crystal structures of RNAP and Gfh1 have been determined separately. Here we report the crystal structure of Thermus thermophilus RNAP complexed with Gfh1. The amino-terminal coiled-coil domain of Gfh1 fully occludes the channel formed between the two central modules of RNAP; this channel would normally be used for nucleotide triphosphate (NTP) entry into the catalytic site. Furthermore, the tip of the coiled-coil domain occupies the NTP beta-gamma phosphate-binding site. The NTP-entry channel is expanded, because the central modules are 'ratcheted' relative to each other by approximately 7 degrees , as compared with the previously reported elongation complexes. This 'ratcheted state' is an alternative structural state, defined by a newly acquired contact between the central modules. Therefore, the shape of Gfh1 is appropriate to maintain RNAP in the ratcheted state. Simultaneously, the ratcheting expands the nucleic-acid-binding channel, and kinks the bridge helix, which connects the central modules. Taken together, the present results reveal that Gfh1 inhibits transcription by preventing NTP binding and freezing RNAP in the alternative structural state. The ratcheted state might also be associated with other aspects of transcription, such as RNAP translocation and transcription termination.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tagami, Shunsuke -- Sekine, Shun-Ichi -- Kumarevel, Thirumananseri -- Hino, Nobumasa -- Murayama, Yuko -- Kamegamori, Syunsuke -- Yamamoto, Masaki -- Sakamoto, Kensaku -- Yokoyama, Shigeyuki -- England -- Nature. 2010 Dec 16;468(7326):978-82. doi: 10.1038/nature09573. Epub 2010 Dec 1.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biophysics and Biochemistry, Graduate School of Science, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21124318" target="_blank"〉PubMed〈/a〉
    Keywords: Bacterial Proteins/*chemistry/*metabolism ; Crystallography, X-Ray ; DNA/chemistry/metabolism ; DNA-Directed RNA Polymerases/*chemistry/*metabolism ; Models, Molecular ; Protein Conformation ; Thermus thermophilus/chemistry/*enzymology ; *Transcription, Genetic
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 42
    facet.materialart.
    Unknown
    Structural basis for receptor recognition of vitamin-B(12)-intrinsic factor complexes (2010)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2010-03-20
    Description: Cobalamin (Cbl, vitamin B(12)) is a bacterial organic compound and an essential coenzyme in mammals, which take it up from the diet. This occurs by the combined action of the gastric intrinsic factor (IF) and the ileal endocytic cubam receptor formed by the 460-kilodalton (kDa) protein cubilin and the 45-kDa transmembrane protein amnionless. Loss of function of any of these proteins ultimately leads to Cbl deficiency in man. Here we present the crystal structure of the complex between IF-Cbl and the cubilin IF-Cbl-binding-region (CUB(5-8)) determined at 3.3 A resolution. The structure provides insight into how several CUB (for 'complement C1r/C1s, Uegf, Bmp1') domains collectively function as modular ligand-binding regions, and how two distant CUB domains embrace the Cbl molecule by binding the two IF domains in a Ca(2+)-dependent manner. This dual-point model provides a probable explanation of how Cbl indirectly induces ligand-receptor coupling. Finally, the comparison of Ca(2+)-binding CUB domains and the low-density lipoprotein (LDL) receptor-type A modules suggests that the electrostatic pairing of a basic ligand arginine/lysine residue with Ca(2+)-coordinating acidic aspartates/glutamates is a common theme of Ca(2+)-dependent ligand-receptor interactions.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Andersen, Christian Brix Folsted -- Madsen, Mette -- Storm, Tina -- Moestrup, Soren K -- Andersen, Gregers R -- England -- Nature. 2010 Mar 18;464(7287):445-8. doi: 10.1038/nature08874.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medical Biochemistry, Aarhus University, 8000 Aarhus C, Denmark.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20237569" target="_blank"〉PubMed〈/a〉
    Keywords: Aspartic Acid/metabolism ; Binding Sites ; Calcium/metabolism ; Crystallography, X-Ray ; Glutamic Acid/metabolism ; Humans ; Intrinsic Factor/*chemistry/*metabolism ; Ligands ; Models, Molecular ; Protein Binding ; Protein Structure, Tertiary ; Receptors, Cell Surface/*chemistry/*metabolism ; Static Electricity ; Vitamin B 12/*chemistry/*metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 43
    facet.materialart.
    Unknown
    Crystal structure of HIV-1 Tat complexed with human P-TEFb (2010)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2010-06-11
    Description: Regulation of the expression of the human immunodeficiency virus (HIV) genome is accomplished in large part by controlling transcription elongation. The viral protein Tat hijacks the host cell's RNA polymerase II elongation control machinery through interaction with the positive transcription elongation factor, P-TEFb, and directs the factor to promote productive elongation of HIV mRNA. Here we describe the crystal structure of the Tat.P-TEFb complex containing HIV-1 Tat, human Cdk9 (also known as CDK9), and human cyclin T1 (also known as CCNT1). Tat adopts a structure complementary to the surface of P-TEFb and makes extensive contacts, mainly with the cyclin T1 subunit of P-TEFb, but also with the T-loop of the Cdk9 subunit. The structure provides a plausible explanation for the tolerance of Tat to sequence variations at certain sites. Importantly, Tat induces significant conformational changes in P-TEFb. This finding lays a foundation for the design of compounds that would specifically inhibit the Tat.P-TEFb complex and block HIV replication.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2885016/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2885016/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tahirov, Tahir H -- Babayeva, Nigar D -- Varzavand, Katayoun -- Cooper, Jeffrey J -- Sedore, Stanley C -- Price, David H -- AI074392/AI/NIAID NIH HHS/ -- GM082923/GM/NIGMS NIH HHS/ -- GM35500/GM/NIGMS NIH HHS/ -- P30CA036727/CA/NCI NIH HHS/ -- P41 RR015301/RR/NCRR NIH HHS/ -- P41 RR015301-075443/RR/NCRR NIH HHS/ -- R01 GM035500/GM/NIGMS NIH HHS/ -- R01 GM035500-20/GM/NIGMS NIH HHS/ -- R01 GM035500-21/GM/NIGMS NIH HHS/ -- R01 GM035500-22/GM/NIGMS NIH HHS/ -- R01 GM035500-23/GM/NIGMS NIH HHS/ -- R01 GM035500-24/GM/NIGMS NIH HHS/ -- R01 GM082923/GM/NIGMS NIH HHS/ -- R01 GM082923-01A2/GM/NIGMS NIH HHS/ -- R01 GM082923-02/GM/NIGMS NIH HHS/ -- R01 GM082923-02S1/GM/NIGMS NIH HHS/ -- R21 AI074392/AI/NIAID NIH HHS/ -- R21 AI074392-01A1/AI/NIAID NIH HHS/ -- R21 AI074392-02/AI/NIAID NIH HHS/ -- R33 AI074392/AI/NIAID NIH HHS/ -- R33 AI074392-03/AI/NIAID NIH HHS/ -- RR-15301/RR/NCRR NIH HHS/ -- England -- Nature. 2010 Jun 10;465(7299):747-51. doi: 10.1038/nature09131.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, Nebraska 68198-7696, USA. ttahirov@unmc.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20535204" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphate/metabolism ; Amino Acid Sequence ; Animals ; Binding Sites ; Crystallography, X-Ray ; Cyclin T/chemistry/metabolism ; Cyclin-Dependent Kinase 9/chemistry/metabolism ; Enzyme Activation ; HIV-1/*chemistry ; Humans ; Models, Molecular ; Molecular Sequence Data ; Positive Transcriptional Elongation Factor B/*chemistry/*metabolism ; Protein Binding ; Protein Conformation ; tat Gene Products, Human Immunodeficiency Virus/*chemistry/genetics/*metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 44
    facet.materialart.
    Unknown
    Encoding multiple unnatural amino acids via evolution of a quadruplet-decoding ribosome (2010)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2010-02-16
    Description: The in vivo, genetically programmed incorporation of designer amino acids allows the properties of proteins to be tailored with molecular precision. The Methanococcus jannaschii tyrosyl-transfer-RNA synthetase-tRNA(CUA) (MjTyrRS-tRNA(CUA)) and the Methanosarcina barkeri pyrrolysyl-tRNA synthetase-tRNA(CUA) (MbPylRS-tRNA(CUA)) orthogonal pairs have been evolved to incorporate a range of unnatural amino acids in response to the amber codon in Escherichia coli. However, the potential of synthetic genetic code expansion is generally limited to the low efficiency incorporation of a single type of unnatural amino acid at a time, because every triplet codon in the universal genetic code is used in encoding the synthesis of the proteome. To encode efficiently many distinct unnatural amino acids into proteins we require blank codons and mutually orthogonal aminoacyl-tRNA synthetase-tRNA pairs that recognize unnatural amino acids and decode the new codons. Here we synthetically evolve an orthogonal ribosome (ribo-Q1) that efficiently decodes a series of quadruplet codons and the amber codon, providing several blank codons on an orthogonal messenger RNA, which it specifically translates. By creating mutually orthogonal aminoacyl-tRNA synthetase-tRNA pairs and combining them with ribo-Q1 we direct the incorporation of distinct unnatural amino acids in response to two of the new blank codons on the orthogonal mRNA. Using this code, we genetically direct the formation of a specific, redox-insensitive, nanoscale protein cross-link by the bio-orthogonal cycloaddition of encoded azide- and alkyne-containing amino acids. Because the synthetase-tRNA pairs used have been evolved to incorporate numerous unnatural amino acids, it will be possible to encode more than 200 unnatural amino acid combinations using this approach. As ribo-Q1 independently decodes a series of quadruplet codons, this work provides foundational technologies for the encoded synthesis and synthetic evolution of unnatural polymers in cells.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Neumann, Heinz -- Wang, Kaihang -- Davis, Lloyd -- Garcia-Alai, Maria -- Chin, Jason W -- MC_U105181009/Medical Research Council/United Kingdom -- MC_UP_A024_1008/Medical Research Council/United Kingdom -- Medical Research Council/United Kingdom -- England -- Nature. 2010 Mar 18;464(7287):441-4. doi: 10.1038/nature08817. Epub 2010 Feb 14.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Medical Research Council Laboratory of Molecular Biology, Hills Road, Cambridge CB2 0QH, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20154731" target="_blank"〉PubMed〈/a〉
    Keywords: Alkynes/metabolism ; Amino Acids/genetics/*metabolism ; Amino Acyl-tRNA Synthetases/genetics/metabolism ; Azides/metabolism ; Biocatalysis/drug effects ; Calmodulin/chemistry/genetics/metabolism ; Codon/*genetics ; Copper/metabolism/pharmacology ; Cyclization/drug effects ; *Directed Molecular Evolution ; *Genetic Code/genetics ; Genetic Engineering/*methods ; Methanococcus ; Models, Molecular ; *Protein Biosynthesis/genetics/physiology ; Protein Conformation ; Protein Engineering/methods ; RNA, Messenger/genetics/metabolism ; RNA, Transfer/genetics/metabolism ; Ribosomes/chemistry/*metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 45
    facet.materialart.
    Unknown
    Self-assembly of spider silk proteins is controlled by a pH-sensitive relay (2010)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2010-05-14
    Description: Nature's high-performance polymer, spider silk, consists of specific proteins, spidroins, with repetitive segments flanked by conserved non-repetitive domains. Spidroins are stored as a highly concentrated fluid dope. On silk formation, intermolecular interactions between repeat regions are established that provide strength and elasticity. How spiders manage to avoid premature spidroin aggregation before self-assembly is not yet established. A pH drop to 6.3 along the spider's spinning apparatus, altered salt composition and shear forces are believed to trigger the conversion to solid silk, but no molecular details are known. Miniature spidroins consisting of a few repetitive spidroin segments capped by the carboxy-terminal domain form metre-long silk-like fibres irrespective of pH. We discovered that incorporation of the amino-terminal domain of major ampullate spidroin 1 from the dragline of the nursery web spider Euprosthenops australis (NT) into mini-spidroins enables immediate, charge-dependent self-assembly at pH values around 6.3, but delays aggregation above pH 7. The X-ray structure of NT, determined to 1.7 A resolution, shows a homodimer of dipolar, antiparallel five-helix bundle subunits that lack homologues. The overall dimeric structure and observed charge distribution of NT is expected to be conserved through spider evolution and in all types of spidroins. Our results indicate a relay-like mechanism through which the N-terminal domain regulates spidroin assembly by inhibiting precocious aggregation during storage, and accelerating and directing self-assembly as the pH is lowered along the spider's silk extrusion duct.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Askarieh, Glareh -- Hedhammar, My -- Nordling, Kerstin -- Saenz, Alejandra -- Casals, Cristina -- Rising, Anna -- Johansson, Jan -- Knight, Stefan D -- England -- Nature. 2010 May 13;465(7295):236-8. doi: 10.1038/nature08962.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry, Oslo University, 1033 Blindern, 0315 Oslo, Norway.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20463740" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Circular Dichroism ; Conserved Sequence ; Crystallography, X-Ray ; Hydrogen-Ion Concentration ; Models, Molecular ; Molecular Sequence Data ; Protein Structure, Tertiary ; Sequence Alignment ; Silk/*chemistry/*metabolism/ultrastructure ; Spiders/*chemistry ; Static Electricity
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 46
    facet.materialart.
    Unknown
    Suppression of inflammation by a synthetic histone mimic (2010)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2010-11-12
    Description: Interaction of pathogens with cells of the immune system results in activation of inflammatory gene expression. This response, although vital for immune defence, is frequently deleterious to the host due to the exaggerated production of inflammatory proteins. The scope of inflammatory responses reflects the activation state of signalling proteins upstream of inflammatory genes as well as signal-induced assembly of nuclear chromatin complexes that support mRNA expression. Recognition of post-translationally modified histones by nuclear proteins that initiate mRNA transcription and support mRNA elongation is a critical step in the regulation of gene expression. Here we present a novel pharmacological approach that targets inflammatory gene expression by interfering with the recognition of acetylated histones by the bromodomain and extra terminal domain (BET) family of proteins. We describe a synthetic compound (I-BET) that by 'mimicking' acetylated histones disrupts chromatin complexes responsible for the expression of key inflammatory genes in activated macrophages, and confers protection against lipopolysaccharide-induced endotoxic shock and bacteria-induced sepsis. Our findings suggest that synthetic compounds specifically targeting proteins that recognize post-translationally modified histones can serve as a new generation of immunomodulatory drugs.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nicodeme, Edwige -- Jeffrey, Kate L -- Schaefer, Uwe -- Beinke, Soren -- Dewell, Scott -- Chung, Chun-Wa -- Chandwani, Rohit -- Marazzi, Ivan -- Wilson, Paul -- Coste, Herve -- White, Julia -- Kirilovsky, Jorge -- Rice, Charles M -- Lora, Jose M -- Prinjha, Rab K -- Lee, Kevin -- Tarakhovsky, Alexander -- England -- Nature. 2010 Dec 23;468(7327):1119-23. doi: 10.1038/nature09589. Epub 2010 Nov 10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Centre de Recherche GSK, 27 Avenue du Quebec, 91140 Villebon Sur Yvette, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21068722" target="_blank"〉PubMed〈/a〉
    Keywords: Acetylation/drug effects ; Animals ; Anti-Inflammatory Agents/chemistry/*pharmacology/therapeutic use ; Benzodiazepines ; Cells, Cultured ; Epigenomics ; Gene Expression Regulation/*drug effects ; Genome-Wide Association Study ; Heterocyclic Compounds with 4 or More Rings/chemistry/*pharmacology/therapeutic ; use ; Histone Deacetylase Inhibitors/pharmacology ; Hydroxamic Acids/pharmacology ; *Inflammation/drug therapy/prevention & control ; Kaplan-Meier Estimate ; Lipopolysaccharides/pharmacology ; Macrophages/*drug effects ; Mice ; Mice, Inbred C57BL ; Models, Molecular ; Protein Structure, Tertiary ; Protein-Serine-Threonine Kinases/metabolism ; Salmonella Infections/drug therapy/immunology/physiopathology/prevention & ; control ; Salmonella typhimurium ; Sepsis/drug therapy/prevention & control ; Shock, Septic/drug therapy/prevention & control
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 47
    facet.materialart.
    Unknown
    Mechanism and regulation of acetylated histone binding by the tandem PHD finger of DPF3b (2010)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2010-07-09
    Description: Histone lysine acetylation and methylation have an important role during gene transcription in a chromatin context. Knowledge concerning the types of protein modules that can interact with acetyl-lysine has so far been limited to bromodomains. Recently, a tandem plant homeodomain (PHD) finger (PHD1-PHD2, or PHD12) of human DPF3b, which functions in association with the BAF chromatin remodelling complex to initiate gene transcription during heart and muscle development, was reported to bind histones H3 and H4 in an acetylation-sensitive manner, making it the first alternative to bromodomains for acetyl-lysine binding. Here we report the structural mechanism of acetylated histone binding by the double PHD fingers of DPF3b. Our three-dimensional solution structures and biochemical analysis of DPF3b highlight the molecular basis of the integrated tandem PHD finger, which acts as one functional unit in the sequence-specific recognition of lysine-14-acetylated histone H3 (H3K14ac). Whereas the interaction with H3 is promoted by acetylation at lysine 14, it is inhibited by methylation at lysine 4, and these opposing influences are important during transcriptional activation of the mouse DPF3b target genes Pitx2 and Jmjd1c. Binding of this tandem protein module to chromatin can thus be regulated by different histone modifications during the initiation of gene transcription.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2901902/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2901902/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zeng, Lei -- Zhang, Qiang -- Li, Side -- Plotnikov, Alexander N -- Walsh, Martin J -- Zhou, Ming-Ming -- R01 CA087658/CA/NCI NIH HHS/ -- R01 CA087658-10/CA/NCI NIH HHS/ -- R01 HG004508/HG/NHGRI NIH HHS/ -- R01 HG004508-02/HG/NHGRI NIH HHS/ -- England -- Nature. 2010 Jul 8;466(7303):258-62. doi: 10.1038/nature09139.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Structural and Chemical Biology, Mount Sinai School of Medicine, 1425 Madison Avenue, Box 1677, New York, New York 10029, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20613843" target="_blank"〉PubMed〈/a〉
    Keywords: Acetylation ; Animals ; Cell Line ; DNA-Binding Proteins/*chemistry/genetics/*metabolism ; Histones/*chemistry/*metabolism ; Humans ; Lysine/chemistry/metabolism ; Mice ; Models, Molecular ; Nuclear Magnetic Resonance, Biomolecular ; Protein Folding ; Structure-Activity Relationship ; Substrate Specificity ; Thermodynamics ; Transcription Factors/*chemistry/genetics/*metabolism ; Transcription, Genetic ; Transcriptional Activation ; Up-Regulation ; *Zinc Fingers
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 48
    facet.materialart.
    Unknown
    Structure of the LexA-DNA complex and implications for SOS box measurement (2010)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2010-08-13
    Description: The eubacterial SOS system is a paradigm of cellular DNA damage and repair, and its activation can contribute to antibiotic resistance. Under normal conditions, LexA represses the transcription of many DNA repair proteins by binding to SOS 'boxes' in their operators. Under genotoxic stress, accumulating complexes of RecA, ATP and single-stranded DNA (ssDNA) activate LexA for autocleavage. To address how LexA recognizes its binding sites, we determined three crystal structures of Escherichia coli LexA in complex with SOS boxes. Here we report the structure of these LexA-DNA complexes. The DNA-binding domains of the LexA dimer interact with the DNA in the classical fashion of a winged helix-turn-helix motif. However, the wings of these two DNA-binding domains bind to the same minor groove of the DNA. These wing-wing contacts may explain why the spacing between the two half-sites of E. coli SOS boxes is invariant.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2921665/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2921665/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhang, Adrianna P P -- Pigli, Ying Z -- Rice, Phoebe A -- GM058827/GM/NIGMS NIH HHS/ -- R01 GM058827/GM/NIGMS NIH HHS/ -- R01 GM058827-09/GM/NIGMS NIH HHS/ -- England -- Nature. 2010 Aug 12;466(7308):883-6. doi: 10.1038/nature09200.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry, The University of Chicago, Chicago, Illinois 60637, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20703307" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Motifs ; Bacterial Proteins/*chemistry/*metabolism ; Base Sequence ; Crystallography, X-Ray ; DNA Damage ; DNA Repair/genetics ; DNA, Bacterial/chemistry/*genetics/*metabolism ; Electrophoretic Mobility Shift Assay ; *Escherichia coli/chemistry/genetics ; Escherichia coli Proteins/chemistry/genetics/metabolism ; Models, Molecular ; Protein Binding ; *Protein Multimerization ; Protein Structure, Tertiary ; Rec A Recombinases/metabolism ; Repressor Proteins/chemistry/metabolism ; SOS Response (Genetics)/*genetics ; Serine Endopeptidases/*chemistry/*metabolism ; Winged-Helix Transcription Factors/chemistry/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 49
    facet.materialart.
    Unknown
    Structural biology: A peep through anion channels (2010)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2010-10-29
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Thomine, Sebastien -- Barbier-Brygoo, Helene -- England -- Nature. 2010 Oct 28;467(7319):1058-9. doi: 10.1038/4671058a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20981091" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Arabidopsis/cytology/genetics/metabolism ; Arabidopsis Proteins/*chemistry/genetics/metabolism ; Bacterial Proteins/*chemistry/genetics/metabolism ; Crystallography, X-Ray ; Haemophilus influenzae/*chemistry/genetics ; Ion Channel Gating ; Membrane Proteins/*chemistry/genetics/metabolism ; Models, Molecular ; Phenylalanine/genetics/metabolism ; Plant Stomata/*metabolism ; Protein Folding ; *Structural Homology, Protein
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 50
    facet.materialart.
    Unknown
    Targeting Bcr-Abl by combining allosteric with ATP-binding-site inhibitors (2010)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2010-01-15
    Description: In an effort to find new pharmacological modalities to overcome resistance to ATP-binding-site inhibitors of Bcr-Abl, we recently reported the discovery of GNF-2, a selective allosteric Bcr-Abl inhibitor. Here, using solution NMR, X-ray crystallography, mutagenesis and hydrogen exchange mass spectrometry, we show that GNF-2 binds to the myristate-binding site of Abl, leading to changes in the structural dynamics of the ATP-binding site. GNF-5, an analogue of GNF-2 with improved pharmacokinetic properties, when used in combination with the ATP-competitive inhibitors imatinib or nilotinib, suppressed the emergence of resistance mutations in vitro, displayed additive inhibitory activity in biochemical and cellular assays against T315I mutant human Bcr-Abl and displayed in vivo efficacy against this recalcitrant mutant in a murine bone-marrow transplantation model. These results show that therapeutically relevant inhibition of Bcr-Abl activity can be achieved with inhibitors that bind to the myristate-binding site and that combining allosteric and ATP-competitive inhibitors can overcome resistance to either agent alone.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2901986/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2901986/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhang, Jianming -- Adrian, Francisco J -- Jahnke, Wolfgang -- Cowan-Jacob, Sandra W -- Li, Allen G -- Iacob, Roxana E -- Sim, Taebo -- Powers, John -- Dierks, Christine -- Sun, Fangxian -- Guo, Gui-Rong -- Ding, Qiang -- Okram, Barun -- Choi, Yongmun -- Wojciechowski, Amy -- Deng, Xianming -- Liu, Guoxun -- Fendrich, Gabriele -- Strauss, Andre -- Vajpai, Navratna -- Grzesiek, Stephan -- Tuntland, Tove -- Liu, Yi -- Bursulaya, Badry -- Azam, Mohammad -- Manley, Paul W -- Engen, John R -- Daley, George Q -- Warmuth, Markus -- Gray, Nathanael S -- R01 CA130876/CA/NCI NIH HHS/ -- R01 CA130876-03/CA/NCI NIH HHS/ -- England -- Nature. 2010 Jan 28;463(7280):501-6. doi: 10.1038/nature08675. Epub 2010 Jan 13.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Dana-Farber Cancer Institute, Harvard Medical School, Department of Cancer Biology, Seeley G. Mudd Building 628, Boston, Massachusetts 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20072125" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antineoplastic Agents/*chemistry/metabolism/*pharmacology ; Antineoplastic Combined Chemotherapy Protocols ; Benzamides ; Binding Sites ; Bone Marrow Transplantation ; Cell Line, Tumor ; Crystallization ; Disease Models, Animal ; Drug Resistance, Neoplasm/*drug effects ; Female ; Fusion Proteins, bcr-abl/*chemistry/genetics/metabolism ; Humans ; Imatinib Mesylate ; Inhibitory Concentration 50 ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug ; therapy/enzymology/*metabolism ; Male ; Mass Spectrometry ; Mice ; Models, Molecular ; Mutation/genetics ; Piperazines/chemistry/pharmacology ; Protein Structure, Tertiary ; Pyrimidines/chemistry/metabolism/pharmacology ; Transplantation, Heterologous
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 51
    facet.materialart.
    Unknown
    Mechanism of folding chamber closure in a group II chaperonin (2010)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2010-01-22
    Description: Group II chaperonins are essential mediators of cellular protein folding in eukaryotes and archaea. These oligomeric protein machines, approximately 1 megadalton, consist of two back-to-back rings encompassing a central cavity that accommodates polypeptide substrates. Chaperonin-mediated protein folding is critically dependent on the closure of a built-in lid, which is triggered by ATP hydrolysis. The structural rearrangements and molecular events leading to lid closure are still unknown. Here we report four single particle cryo-electron microscopy (cryo-EM) structures of Mm-cpn, an archaeal group II chaperonin, in the nucleotide-free (open) and nucleotide-induced (closed) states. The 4.3 A resolution of the closed conformation allowed building of the first ever atomic model directly from the single particle cryo-EM density map, in which we were able to visualize the nucleotide and more than 70% of the side chains. The model of the open conformation was obtained by using the deformable elastic network modelling with the 8 A resolution open-state cryo-EM density restraints. Together, the open and closed structures show how local conformational changes triggered by ATP hydrolysis lead to an alteration of intersubunit contacts within and across the rings, ultimately causing a rocking motion that closes the ring. Our analyses show that there is an intricate and unforeseen set of interactions controlling allosteric communication and inter-ring signalling, driving the conformational cycle of group II chaperonins. Beyond this, we anticipate that our methodology of combining single particle cryo-EM and computational modelling will become a powerful tool in the determination of atomic details involved in the dynamic processes of macromolecular machines in solution.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2834796/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2834796/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhang, Junjie -- Baker, Matthew L -- Schroder, Gunnar F -- Douglas, Nicholai R -- Reissmann, Stefanie -- Jakana, Joanita -- Dougherty, Matthew -- Fu, Caroline J -- Levitt, Michael -- Ludtke, Steven J -- Frydman, Judith -- Chiu, Wah -- P41 RR002250/RR/NCRR NIH HHS/ -- P41 RR002250-23/RR/NCRR NIH HHS/ -- P41 RR002250-237254/RR/NCRR NIH HHS/ -- P41 RR002250-24/RR/NCRR NIH HHS/ -- P41 RR002250-247897/RR/NCRR NIH HHS/ -- PN2 EY016525/EY/NEI NIH HHS/ -- PN2 EY016525-02S1/EY/NEI NIH HHS/ -- PN2 EY016525-03/EY/NEI NIH HHS/ -- PN2 EY016525-04/EY/NEI NIH HHS/ -- PN2 EY016525-05/EY/NEI NIH HHS/ -- R01 GM063817/GM/NIGMS NIH HHS/ -- R01 GM079429/GM/NIGMS NIH HHS/ -- R01 GM079429-03/GM/NIGMS NIH HHS/ -- R01 GM080139/GM/NIGMS NIH HHS/ -- R01 GM080139-03/GM/NIGMS NIH HHS/ -- R01 GM080139-04/GM/NIGMS NIH HHS/ -- R90 DK071504/DK/NIDDK NIH HHS/ -- R90 DK071504-03/DK/NIDDK NIH HHS/ -- T32 GM007276-30/GM/NIGMS NIH HHS/ -- T32 GM007276-31/GM/NIGMS NIH HHS/ -- England -- Nature. 2010 Jan 21;463(7279):379-83. doi: 10.1038/nature08701.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Graduate Program in Structural and Computational Biology and Molecular Biophysics, Baylor College of Medicine, Houston, Texas 77030, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20090755" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphate/chemistry/metabolism/pharmacology ; Allosteric Regulation ; Binding Sites ; Cryoelectron Microscopy ; Group II Chaperonins/*chemistry/*metabolism/ultrastructure ; Hydrolysis/drug effects ; Methanococcus/*chemistry ; Models, Molecular ; Protein Binding ; Protein Conformation/drug effects ; *Protein Folding ; Protein Subunits/chemistry/metabolism ; Structure-Activity Relationship
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 52
    facet.materialart.
    Unknown
    Structure of the torque ring of the flagellar motor and the molecular basis for rotational switching (2010)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2010-08-03
    Description: The flagellar motor drives the rotation of flagellar filaments at hundreds of revolutions per second, efficiently propelling bacteria through viscous media. The motor uses the potential energy from an electrochemical gradient of cations across the cytoplasmic membrane to generate torque. A rapid switch from anticlockwise to clockwise rotation determines whether a bacterium runs smoothly forward or tumbles to change its trajectory. A protein called FliG forms a ring in the rotor of the flagellar motor that is involved in the generation of torque through an interaction with the cation-channel-forming stator subunit MotA. FliG has been suggested to adopt distinct conformations that induce switching but these structural changes and the molecular mechanism of switching are unknown. Here we report the molecular structure of the full-length FliG protein, identify conformational changes that are involved in rotational switching and uncover the structural basis for the formation of the FliG torque ring. This allows us to propose a model of the complete ring and switching mechanism in which conformational changes in FliG reverse the electrostatic charges involved in torque generation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3159035/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3159035/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lee, Lawrence K -- Ginsburg, Michael A -- Crovace, Claudia -- Donohoe, Mhairi -- Stock, Daniela -- MC_U105170645/Medical Research Council/United Kingdom -- P41 RR007707/RR/NCRR NIH HHS/ -- P41 RR007707-17/RR/NCRR NIH HHS/ -- RR007707/RR/NCRR NIH HHS/ -- Y1-CO-1020/CO/NCI NIH HHS/ -- Y1-GM-1104/GM/NIGMS NIH HHS/ -- Medical Research Council/United Kingdom -- England -- Nature. 2010 Aug 19;466(7309):996-1000. doi: 10.1038/nature09300. Epub 2010 Aug 1.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Structural and Computational Biology Division, The Victor Chang Cardiac Research Institute, Lowy Packer Building, 405 Liverpool Street, Darlinghurst, New South Wales 2010, Australia.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20676082" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Bacterial Proteins/*chemistry/genetics/*metabolism ; Flagella/*chemistry/genetics/*physiology ; Models, Molecular ; Molecular Motor Proteins/*chemistry/genetics/metabolism ; Molecular Sequence Data ; Mutation ; Protein Conformation ; Protein Multimerization ; Protein Structure, Tertiary ; *Rotation ; Static Electricity ; Structure-Activity Relationship ; Thermotoga maritima/chemistry ; *Torque
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 53
    facet.materialart.
    Unknown
    Structure and mechanism of the S component of a bacterial ECF transporter (2010)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2010-10-26
    Description: The energy-coupling factor (ECF) transporters, responsible for vitamin uptake in prokaryotes, are a unique family of membrane transporters. Each ECF transporter contains a membrane-embedded, substrate-binding protein (known as the S component), an energy-coupling module that comprises two ATP-binding proteins (known as the A and A' components) and a transmembrane protein (known as the T component). The structure and transport mechanism of the ECF family remain unknown. Here we report the crystal structure of RibU, the S component of the ECF-type riboflavin transporter from Staphylococcus aureus at 3.6-A resolution. RibU contains six transmembrane segments, adopts a previously unreported transporter fold and contains a riboflavin molecule bound to the L1 loop and the periplasmic portion of transmembrane segments 4-6. Structural analysis reveals the essential ligand-binding residues, identifies the putative transport path and, with sequence alignment, uncovers conserved structural features and suggests potential mechanisms of action among the ECF transporters.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhang, Peng -- Wang, Jiawei -- Shi, Yigong -- R01 GM084964/GM/NIGMS NIH HHS/ -- England -- Nature. 2010 Dec 2;468(7324):717-20. doi: 10.1038/nature09488. Epub 2010 Oct 24.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology, Lewis Thomas Laboratory, Princeton University, Princeton, New Jersey 08544, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20972419" target="_blank"〉PubMed〈/a〉
    Keywords: Bacterial Proteins/*chemistry/*metabolism ; Binding Sites ; Conserved Sequence ; Crystallography, X-Ray ; Ligands ; Membrane Transport Proteins/*chemistry/classification/*metabolism ; Models, Molecular ; Movement ; Periplasm/metabolism ; Protein Folding ; Protein Structure, Tertiary ; Riboflavin/chemistry/*metabolism ; Sequence Alignment ; Staphylococcus aureus/*chemistry ; Substrate Specificity
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 54
    facet.materialart.
    Unknown
    Structural basis for semaphorin signalling through the plexin receptor (2010)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2010-10-01
    Description: Semaphorins and their receptor plexins constitute a pleiotropic cell-signalling system that is used in a wide variety of biological processes, and both protein families have been implicated in numerous human diseases. The binding of soluble or membrane-anchored semaphorins to the membrane-distal region of the plexin ectodomain activates plexin's intrinsic GTPase-activating protein (GAP) at the cytoplasmic region, ultimately modulating cellular adhesion behaviour. However, the structural mechanism underlying the receptor activation remains largely unknown. Here we report the crystal structures of the semaphorin 6A (Sema6A) receptor-binding fragment and the plexin A2 (PlxnA2) ligand-binding fragment in both their pre-signalling (that is, before binding) and signalling (after complex formation) states. Before binding, the Sema6A ectodomain was in the expected 'face-to-face' homodimer arrangement, similar to that adopted by Sema3A and Sema4D, whereas PlxnA2 was in an unexpected 'head-on' homodimer arrangement. In contrast, the structure of the Sema6A-PlxnA2 signalling complex revealed a 2:2 heterotetramer in which the two PlxnA2 monomers dissociated from one another and docked onto the top face of the Sema6A homodimer using the same interface as the head-on homodimer, indicating that plexins undergo 'partner exchange'. Cell-based activity measurements using mutant ligands/receptors confirmed that the Sema6A face-to-face dimer arrangement is physiologically relevant and is maintained throughout signalling events. Thus, homodimer-to-heterodimer transitions of cell-surface plexin that result in a specific orientation of its molecular axis relative to the membrane may constitute the structural mechanism by which the ligand-binding 'signal' is transmitted to the cytoplasmic region, inducing GAP domain rearrangements and activation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nogi, Terukazu -- Yasui, Norihisa -- Mihara, Emiko -- Matsunaga, Yukiko -- Noda, Masanori -- Yamashita, Naoya -- Toyofuku, Toshihiko -- Uchiyama, Susumu -- Goshima, Yoshio -- Kumanogoh, Atsushi -- Takagi, Junichi -- England -- Nature. 2010 Oct 28;467(7319):1123-7. doi: 10.1038/nature09473. Epub 2010 Sep 29.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Protein Synthesis and Expression, Institute for Protein Research, Osaka University, 3-2 Yamadaoka, Suita, Osaka 565-0871, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20881961" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Binding Sites ; Crystallography, X-Ray ; HEK293 Cells ; Humans ; Ligands ; Mice ; Models, Molecular ; Molecular Sequence Data ; Nerve Tissue Proteins/*chemistry/genetics/*metabolism ; Protein Binding ; Protein Structure, Tertiary ; Receptors, Cell Surface/*chemistry/genetics/*metabolism ; Semaphorins/*chemistry/genetics/*metabolism ; *Signal Transduction ; Structure-Activity Relationship
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 55
    facet.materialart.
    Unknown
    Crystal structure of the alpha(6)beta(6) holoenzyme of propionyl-coenzyme A carboxylase (2010)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2010-08-21
    Description: Propionyl-coenzyme A carboxylase (PCC), a mitochondrial biotin-dependent enzyme, is essential for the catabolism of the amino acids Thr, Val, Ile and Met, cholesterol and fatty acids with an odd number of carbon atoms. Deficiencies in PCC activity in humans are linked to the disease propionic acidaemia, an autosomal recessive disorder that can be fatal in infants. The holoenzyme of PCC is an alpha(6)beta(6) dodecamer, with a molecular mass of 750 kDa. The alpha-subunit contains the biotin carboxylase (BC) and biotin carboxyl carrier protein (BCCP) domains, whereas the beta-subunit supplies the carboxyltransferase (CT) activity. Here we report the crystal structure at 3.2-A resolution of a bacterial PCC alpha(6)beta(6) holoenzyme as well as cryo-electron microscopy (cryo-EM) reconstruction at 15-A resolution demonstrating a similar structure for human PCC. The structure defines the overall architecture of PCC and reveals unexpectedly that the alpha-subunits are arranged as monomers in the holoenzyme, decorating a central beta(6) hexamer. A hitherto unrecognized domain in the alpha-subunit, formed by residues between the BC and BCCP domains, is crucial for interactions with the beta-subunit. We have named it the BT domain. The structure reveals for the first time the relative positions of the BC and CT active sites in the holoenzyme. They are separated by approximately 55 A, indicating that the entire BCCP domain must translocate during catalysis. The BCCP domain is located in the active site of the beta-subunit in the current structure, providing insight for its involvement in the CT reaction. The structural information establishes a molecular basis for understanding the large collection of disease-causing mutations in PCC and is relevant for the holoenzymes of other biotin-dependent carboxylases, including 3-methylcrotonyl-CoA carboxylase (MCC) and eukaryotic acetyl-CoA carboxylase (ACC).〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2925307/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2925307/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Huang, Christine S -- Sadre-Bazzaz, Kianoush -- Shen, Yang -- Deng, Binbin -- Zhou, Z Hong -- Tong, Liang -- AI069015/AI/NIAID NIH HHS/ -- DK067238/DK/NIDDK NIH HHS/ -- GM071940/GM/NIGMS NIH HHS/ -- GM08281/GM/NIGMS NIH HHS/ -- P30 EB009998/EB/NIBIB NIH HHS/ -- R01 AI069015/AI/NIAID NIH HHS/ -- R01 AI069015-04/AI/NIAID NIH HHS/ -- R01 DK067238/DK/NIDDK NIH HHS/ -- R01 DK067238-07/DK/NIDDK NIH HHS/ -- R01 GM071940/GM/NIGMS NIH HHS/ -- R01 GM071940-05/GM/NIGMS NIH HHS/ -- T32 GM008281/GM/NIGMS NIH HHS/ -- T32 GM008281-23/GM/NIGMS NIH HHS/ -- England -- Nature. 2010 Aug 19;466(7309):1001-5. doi: 10.1038/nature09302.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biological Sciences, Columbia University, New York, New York 10027, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20725044" target="_blank"〉PubMed〈/a〉
    Keywords: Acetyl-CoA Carboxylase/chemistry/metabolism/ultrastructure ; Biocatalysis ; Biotin/metabolism ; Carbon-Nitrogen Ligases/chemistry/metabolism/ultrastructure ; Carrier Proteins/chemistry/metabolism/ultrastructure ; Catalytic Domain ; *Cryoelectron Microscopy ; Crystallography, X-Ray ; Fatty Acid Synthase, Type II ; Holoenzymes/*chemistry/genetics/metabolism/*ultrastructure ; Humans ; Methylmalonyl-CoA Decarboxylase/*chemistry/genetics/metabolism/*ultrastructure ; Models, Molecular ; Mutation/genetics ; Propionic Acidemia/enzymology/genetics ; Protein Binding ; Protein Structure, Quaternary ; Protein Structure, Tertiary ; Protein Subunits/chemistry/metabolism ; Rhodobacteraceae/enzymology ; Structure-Activity Relationship
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 56
    facet.materialart.
    Unknown
    Single-molecule dynamics of gating in a neurotransmitter transporter homologue (2010)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2010-05-14
    Description: Neurotransmitter:Na(+) symporters (NSS) remove neurotransmitters from the synapse in a reuptake process that is driven by the Na(+) gradient. Drugs that interfere with this reuptake mechanism, such as cocaine and antidepressants, profoundly influence behaviour and mood. To probe the nature of the conformational changes that are associated with substrate binding and transport, we have developed a single-molecule fluorescence imaging assay and combined it with functional and computational studies of the prokaryotic NSS homologue LeuT. Here we show molecular details of the modulation of intracellular gating of LeuT by substrates and inhibitors, as well as by mutations that alter binding, transport or both. Our direct observations of single-molecule transitions, reflecting structural dynamics of the intracellular region of the transporter that might be masked by ensemble averaging or suppressed under crystallographic conditions, are interpreted in the context of an allosteric mechanism that couples ion and substrate binding to transport.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2940119/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2940119/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhao, Yongfang -- Terry, Daniel -- Shi, Lei -- Weinstein, Harel -- Blanchard, Scott C -- Javitch, Jonathan A -- DA022413/DA/NIDA NIH HHS/ -- DA023694/DA/NIDA NIH HHS/ -- DA12408/DA/NIDA NIH HHS/ -- DA17293/DA/NIDA NIH HHS/ -- K05 DA022413/DA/NIDA NIH HHS/ -- K99 DA023694/DA/NIDA NIH HHS/ -- K99 DA023694-02/DA/NIDA NIH HHS/ -- R01 DA017293/DA/NIDA NIH HHS/ -- England -- Nature. 2010 May 13;465(7295):188-93. doi: 10.1038/nature09057.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Molecular Recognition, Columbia University College of Physicians and Surgeons, 630 W. 168th, New York, New York 10032, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20463731" target="_blank"〉PubMed〈/a〉
    Keywords: Alanine/metabolism ; Allosteric Regulation ; Aquifoliaceae/*chemistry ; Bacterial Proteins/*chemistry/genetics/*metabolism ; Crystallography, X-Ray ; Cysteine/chemistry/metabolism ; Escherichia coli ; Fluorescence Resonance Energy Transfer ; Leucine/metabolism ; Models, Molecular ; Molecular Dynamics Simulation ; Plasma Membrane Neurotransmitter Transport ; Proteins/*chemistry/genetics/*metabolism ; Protein Conformation ; Sodium/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 57
    facet.materialart.
    Unknown
    G domain dimerization controls dynamin's assembly-stimulated GTPase activity (2010)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2010-04-30
    Description: Dynamin is an atypical GTPase that catalyses membrane fission during clathrin-mediated endocytosis. The mechanisms of dynamin's basal and assembly-stimulated GTP hydrolysis are unknown, though both are indirectly influenced by the GTPase effector domain (GED). Here we present the 2.0 A resolution crystal structure of a human dynamin 1-derived minimal GTPase-GED fusion protein, which was dimeric in the presence of the transition state mimic GDP.AlF(4)(-).The structure reveals dynamin's catalytic machinery and explains how assembly-stimulated GTP hydrolysis is achieved through G domain dimerization. A sodium ion present in the active site suggests that dynamin uses a cation to compensate for the developing negative charge in the transition state in the absence of an arginine finger. Structural comparison to the rat dynamin G domain reveals key conformational changes that promote G domain dimerization and stimulated hydrolysis. The structure of the GTPase-GED fusion protein dimer provides insight into the mechanisms underlying dynamin-catalysed membrane fission.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2879890/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2879890/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chappie, Joshua S -- Acharya, Sharmistha -- Leonard, Marilyn -- Schmid, Sandra L -- Dyda, Fred -- F31 MH081419/MH/NIMH NIH HHS/ -- F31 MH081419-02/MH/NIMH NIH HHS/ -- GM42455/GM/NIGMS NIH HHS/ -- MH081419/MH/NIMH NIH HHS/ -- MH61345/MH/NIMH NIH HHS/ -- R01 GM042455/GM/NIGMS NIH HHS/ -- R01 GM042455-20/GM/NIGMS NIH HHS/ -- R37 MH061345/MH/NIMH NIH HHS/ -- R37 MH061345-10/MH/NIMH NIH HHS/ -- Intramural NIH HHS/ -- England -- Nature. 2010 May 27;465(7297):435-40. doi: 10.1038/nature09032. Epub 2010 Apr 28.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, Maryland 20892, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20428113" target="_blank"〉PubMed〈/a〉
    Keywords: Aluminum Compounds/metabolism ; Amino Acid Sequence ; Biocatalysis ; Catalytic Domain/genetics ; Conserved Sequence ; Crystallography, X-Ray ; Dynamin I/*chemistry/genetics/*metabolism ; Enzyme Activation ; Fluorides/metabolism ; GTP Phosphohydrolases/*chemistry/genetics/*metabolism ; Guanosine Diphosphate/analogs & derivatives/metabolism ; Humans ; Hydrolysis ; Models, Molecular ; *Protein Multimerization ; Protein Structure, Quaternary ; Protein Structure, Tertiary ; Sodium/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 58
    facet.materialart.
    Unknown
    Dynamics and mechanism of repair of ultraviolet-induced (6-4) photoproduct by photolyase (2010)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2010-07-27
    Description: One of the detrimental effects of ultraviolet radiation on DNA is the formation of the (6-4) photoproduct, 6-4PP, between two adjacent pyrimidine rings. This lesion interferes with replication and transcription, and may result in mutation and cell death. In many organisms, a flavoenzyme called photolyase uses blue light energy to repair the 6-4PP (ref. 3). The molecular mechanism of the repair reaction is poorly understood. Here, we use ultrafast spectroscopy to show that the key step in the repair photocycle is acyclic proton transfer between the enzyme and the substrate. By femtosecond synchronization of the enzymatic dynamics with the repair function, we followed the function evolution and observed direct electron transfer from the excited flavin cofactor to the 6-4PP in 225 picoseconds, but surprisingly fast back electron transfer in 50 picoseconds without repair. We found that the catalytic proton transfer between a histidine residue in the active site and the 6-4PP, induced by the initial photoinduced electron transfer from the excited flavin cofactor to 6-4PP, occurs in 425 picoseconds and leads to 6-4PP repair in tens of nanoseconds. These key dynamics define the repair photocycle and explain the underlying molecular mechanism of the enzyme's modest efficiency.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3018752/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3018752/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Li, Jiang -- Liu, Zheyun -- Tan, Chuang -- Guo, Xunmin -- Wang, Lijuan -- Sancar, Aziz -- Zhong, Dongping -- GM074813/GM/NIGMS NIH HHS/ -- P30 ES010126/ES/NIEHS NIH HHS/ -- R01 GM031082/GM/NIGMS NIH HHS/ -- R01 GM074813/GM/NIGMS NIH HHS/ -- R01 GM074813-04/GM/NIGMS NIH HHS/ -- R01 HG002779-05/HG/NHGRI NIH HHS/ -- R01 HG002779-06/HG/NHGRI NIH HHS/ -- R01 LM006845/LM/NLM NIH HHS/ -- England -- Nature. 2010 Aug 12;466(7308):887-890. doi: 10.1038/nature09192.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physics, Program of Biophysics, The Ohio State University, Columbus, Ohio 43210, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20657578" target="_blank"〉PubMed〈/a〉
    Keywords: Absorption ; Animals ; Arabidopsis/*enzymology/genetics ; Biocatalysis ; DNA Damage ; *DNA Repair/radiation effects ; Deoxyribodipyrimidine Photo-Lyase/chemistry/genetics/*metabolism ; Drosophila melanogaster/enzymology ; Electrons ; Flavins/chemistry/metabolism ; Histidine/genetics/metabolism ; Kinetics ; Models, Molecular ; Protons ; Pyrimidine Dimers/chemistry/*metabolism/*radiation effects ; Time Factors ; *Ultraviolet Rays
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 59
    facet.materialart.
    Unknown
    Structural changes of envelope proteins during alphavirus fusion (2010)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2010-12-03
    Description: Alphaviruses are enveloped RNA viruses that have a diameter of about 700 A and can be lethal human pathogens. Entry of virus into host cells by endocytosis is controlled by two envelope glycoproteins, E1 and E2. The E2-E1 heterodimers form 80 trimeric spikes on the icosahedral virus surface, 60 with quasi-three-fold symmetry and 20 coincident with the icosahedral three-fold axes arranged with T = 4 quasi-symmetry. The E1 glycoprotein has a hydrophobic fusion loop at one end and is responsible for membrane fusion. The E2 protein is responsible for receptor binding and protects the fusion loop at neutral pH. The lower pH in the endosome induces the virions to undergo an irreversible conformational change in which E2 and E1 dissociate and E1 forms homotrimers, triggering fusion of the viral membrane with the endosomal membrane and then releasing the viral genome into the cytoplasm. Here we report the structure of an alphavirus spike, crystallized at low pH, representing an intermediate in the fusion process and clarifying the maturation process. The trimer of E2-E1 in the crystal structure is similar to the spikes in the neutral pH virus except that the E2 middle region is disordered, exposing the fusion loop. The amino- and carboxy-terminal domains of E2 each form immunoglobulin-like folds, consistent with the receptor attachment properties of E2.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3057476/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3057476/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Li, Long -- Jose, Joyce -- Xiang, Ye -- Kuhn, Richard J -- Rossmann, Michael G -- P01 AI055672/AI/NIAID NIH HHS/ -- P01 AI055672-07/AI/NIAID NIH HHS/ -- England -- Nature. 2010 Dec 2;468(7324):705-8. doi: 10.1038/nature09546.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biological Sciences, Purdue University, 915 W. State Street, West Lafayette, Indiana 47907-2054, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21124457" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Line ; Cryoelectron Microscopy ; Crystallography, X-Ray ; Drosophila melanogaster ; Endosomes/metabolism ; Hydrogen-Ion Concentration ; Hydrophobic and Hydrophilic Interactions ; Membrane Fusion ; Membrane Glycoproteins/chemistry/metabolism ; Models, Molecular ; Protein Multimerization ; Protein Structure, Quaternary ; Protein Structure, Tertiary ; Receptors, Virus/metabolism ; Sindbis Virus/*chemistry/*metabolism ; Viral Envelope Proteins/*chemistry/*metabolism ; Viral Fusion Proteins/chemistry/metabolism ; Virion/chemistry/metabolism ; *Virus Internalization
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 60
    facet.materialart.
    Unknown
    Fructose 1,6-bisphosphate aldolase/phosphatase may be an ancestral gluconeogenic enzyme (2010)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2010-03-30
    Description: Most archaeal groups and deeply branching bacterial lineages harbour thermophilic organisms with a chemolithoautotrophic metabolism. They live at high temperatures in volcanic habitats at the expense of inorganic substances, often under anoxic conditions. These autotrophic organisms use diverse carbon dioxide fixation mechanisms generating acetyl-coenzyme A, from which gluconeogenesis must start. Here we show that virtually all archaeal groups as well as the deeply branching bacterial lineages contain a bifunctional fructose 1,6-bisphosphate (FBP) aldolase/phosphatase with both FBP aldolase and FBP phosphatase activity. This enzyme is missing in most other Bacteria and in Eukaryota, and is heat-stabile even in mesophilic marine Crenarchaeota. Its bifunctionality ensures that heat-labile triosephosphates are quickly removed and trapped in stabile fructose 6-phosphate, rendering gluconeogenesis unidirectional. We propose that this highly conserved, heat-stabile and bifunctional FBP aldolase/phosphatase represents the pace-making ancestral gluconeogenic enzyme, and that in evolution gluconeogenesis preceded glycolysis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Say, Rafael F -- Fuchs, Georg -- England -- Nature. 2010 Apr 15;464(7291):1077-81. doi: 10.1038/nature08884. Epub 2010 Mar 28.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Mikrobiologie, Fakultat Biologie, Universitat Freiburg, Schanzlestrasse 1, D-79104 Freiburg, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20348906" target="_blank"〉PubMed〈/a〉
    Keywords: Archaea/enzymology ; Bacteria/enzymology ; Biocatalysis ; Catalytic Domain ; Enzyme Stability ; *Evolution, Molecular ; Fructose-Bisphosphate Aldolase/chemistry/*metabolism ; Fructosediphosphates/chemistry/*metabolism ; Fructosephosphates/metabolism ; *Gluconeogenesis ; Glycolysis ; Hot Temperature ; Models, Molecular ; Origin of Life ; Phosphoric Monoester Hydrolases/chemistry/*metabolism ; Phylogeny ; Protein Conformation ; Ribosomal Proteins/classification
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 61
    facet.materialart.
    Unknown
    Recognition of a signal peptide by the signal recognition particle (2010)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2010-04-07
    Description: Targeting of proteins to appropriate subcellular compartments is a crucial process in all living cells. Secretory and membrane proteins usually contain an amino-terminal signal peptide, which is recognized by the signal recognition particle (SRP) when nascent polypeptide chains emerge from the ribosome. The SRP-ribosome nascent chain complex is then targeted through its GTP-dependent interaction with SRP receptor to the protein-conducting channel on endoplasmic reticulum membrane in eukaryotes or plasma membrane in bacteria. A universally conserved component of SRP (refs 1, 2), SRP54 or its bacterial homologue, fifty-four homologue (Ffh), binds the signal peptides, which have a highly divergent sequence divisible into a positively charged n-region, an h-region commonly containing 8-20 hydrophobic residues and a polar c-region. No structure has been reported that exemplifies SRP54 binding of any signal sequence. Here we have produced a fusion protein between Sulfolobus solfataricus SRP54 (Ffh) and a signal peptide connected via a flexible linker. This fusion protein oligomerizes in solution through interaction between the SRP54 and signal peptide moieties belonging to different chains, and it is functional, as demonstrated by its ability to bind SRP RNA and SRP receptor FtsY. We present the crystal structure at 3.5 A resolution of an SRP54-signal peptide complex in the dimer, which reveals how a signal sequence is recognized by SRP54.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2897128/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2897128/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Janda, Claudia Y -- Li, Jade -- Oubridge, Chris -- Hernandez, Helena -- Robinson, Carol V -- Nagai, Kiyoshi -- MC_U105184330/Medical Research Council/United Kingdom -- U.1051.04.016(78933)/Medical Research Council/United Kingdom -- Medical Research Council/United Kingdom -- England -- Nature. 2010 May 27;465(7297):507-10. doi: 10.1038/nature08870. Epub 2010 Apr 4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 0QH, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20364120" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Bacterial Proteins/metabolism ; Crystallography, X-Ray ; Mass Spectrometry ; Models, Molecular ; Molecular Sequence Data ; Protein Binding ; Protein Multimerization ; Protein Sorting Signals/*physiology ; Protein Structure, Quaternary ; Protein Structure, Tertiary ; Receptors, Cytoplasmic and Nuclear/metabolism ; Receptors, Virus/metabolism ; Recombinant Fusion Proteins/chemistry/metabolism ; Signal Recognition Particle/*chemistry/*metabolism ; Structure-Activity Relationship ; Sulfolobus solfataricus/*chemistry
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 62
    facet.materialart.
    Unknown
    Direct visualization of secondary structures of F-actin by electron cryomicroscopy (2010)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2010-09-17
    Description: F-actin is a helical assembly of actin, which is a component of muscle fibres essential for contraction and has a crucial role in numerous cellular processes, such as the formation of lamellipodia and filopodia, as the most abundant component and regulator of cytoskeletons by dynamic assembly and disassembly (from G-actin to F-actin and vice versa). Actin is a ubiquitous protein and is involved in important biological functions, but the definitive high-resolution structure of F-actin remains unknown. Although a recent atomic model well reproduced X-ray fibre diffraction intensity data from a highly oriented liquid-crystalline sol specimen, its refinement without experimental phase information has certain limitations. Direct visualization of the structure by electron cryomicroscopy, however, has been difficult because it is relatively thin and flexible. Here we report the F-actin structure at 6.6 A resolution, made obtainable by recent advances in electron cryomicroscopy. The density map clearly resolves all the secondary structures of G-actin, such as alpha-helices, beta-structures and loops, and makes unambiguous modelling and refinement possible. Complex domain motions that open the nucleotide-binding pocket on F-actin formation, specific D-loop and terminal conformations, and relatively tight axial but markedly loose interprotofilament interactions hydrophilic in nature are revealed in the F-actin model, and all seem to be important for dynamic functions of actin.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fujii, Takashi -- Iwane, Atsuko H -- Yanagida, Toshio -- Namba, Keiichi -- England -- Nature. 2010 Oct 7;467(7316):724-8. doi: 10.1038/nature09372. Epub 2010 Sep 15.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Graduate School of Frontier Biosciences, Osaka University, 1-3 Yamadaoka, Suita, Osaka 565-0871, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20844487" target="_blank"〉PubMed〈/a〉
    Keywords: Actins/*chemistry/*ultrastructure ; Animals ; *Cryoelectron Microscopy ; Crystallography, X-Ray ; Hydrogen Bonding ; Models, Molecular ; Protein Structure, Secondary ; Protein Subunits ; Rabbits ; Static Electricity
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 63
    facet.materialart.
    Unknown
    Homologue structure of the SLAC1 anion channel for closing stomata in leaves (2010)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2010-10-29
    Description: The plant SLAC1 anion channel controls turgor pressure in the aperture-defining guard cells of plant stomata, thereby regulating the exchange of water vapour and photosynthetic gases in response to environmental signals such as drought or high levels of carbon dioxide. Here we determine the crystal structure of a bacterial homologue (Haemophilus influenzae) of SLAC1 at 1.20 A resolution, and use structure-inspired mutagenesis to analyse the conductance properties of SLAC1 channels. SLAC1 is a symmetrical trimer composed from quasi-symmetrical subunits, each having ten transmembrane helices arranged from helical hairpin pairs to form a central five-helix transmembrane pore that is gated by an extremely conserved phenylalanine residue. Conformational features indicate a mechanism for control of gating by kinase activation, and electrostatic features of the pore coupled with electrophysiological characteristics indicate that selectivity among different anions is largely a function of the energetic cost of ion dehydration.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3548404/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3548404/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chen, Yu-Hang -- Hu, Lei -- Punta, Marco -- Bruni, Renato -- Hillerich, Brandan -- Kloss, Brian -- Rost, Burkhard -- Love, James -- Siegelbaum, Steven A -- Hendrickson, Wayne A -- R01 GM034102/GM/NIGMS NIH HHS/ -- U54 GM075026/GM/NIGMS NIH HHS/ -- U54 GM095315/GM/NIGMS NIH HHS/ -- England -- Nature. 2010 Oct 28;467(7319):1074-80. doi: 10.1038/nature09487.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Molecular Biophysics, Columbia University, New York, New York 10032, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20981093" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Arabidopsis/genetics/metabolism ; Arabidopsis Proteins/*chemistry ; Bacterial Proteins/*chemistry/genetics/metabolism ; Crystallography, X-Ray ; Electric Conductivity ; Haemophilus influenzae/*chemistry/genetics ; Ion Channel Gating ; Membrane Proteins/*chemistry ; Models, Molecular ; Molecular Sequence Data ; Oocytes/metabolism ; Phenylalanine/chemistry/metabolism ; Plant Stomata/*metabolism ; Static Electricity ; *Structural Homology, Protein ; Substrate Specificity ; Xenopus laevis
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 64
    facet.materialart.
    Unknown
    Structural basis for the coupling between activation and inactivation gates in K(+) channels (2010)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2010-07-09
    Description: The coupled interplay between activation and inactivation gating is a functional hallmark of K(+) channels. This coupling has been experimentally demonstrated through ion interaction effects and cysteine accessibility, and is associated with a well defined boundary of energetically coupled residues. The structure of the K(+) channel KcsA in its fully open conformation, in addition to four other partial channel openings, richly illustrates the structural basis of activation-inactivation gating. Here, we identify the mechanistic principles by which movements on the inner bundle gate trigger conformational changes at the selectivity filter, leading to the non-conductive C-type inactivated state. Analysis of a series of KcsA open structures suggests that, as a consequence of the hinge-bending and rotation of the TM2 helix, the aromatic ring of Phe 103 tilts towards residues Thr 74 and Thr 75 in the pore-helix and towards Ile 100 in the neighbouring subunit. This allows the network of hydrogen bonds among residues Trp 67, Glu 71 and Asp 80 to destabilize the selectivity filter, allowing entry to its non-conductive conformation. Mutations at position 103 have a size-dependent effect on gating kinetics: small side-chain substitutions F103A and F103C severely impair inactivation kinetics, whereas larger side chains such as F103W have more subtle effects. This suggests that the allosteric coupling between the inner helical bundle and the selectivity filter might rely on straightforward mechanical deformation propagated through a network of steric contacts. Average interactions calculated from molecular dynamics simulations show favourable open-state interaction-energies between Phe 103 and the surrounding residues. We probed similar interactions in the Shaker K(+) channel where inactivation was impaired in the mutant I470A. We propose that side-chain rearrangements at position 103 mechanically couple activation and inactivation in KcsA and a variety of other K(+) channels.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3033755/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3033755/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cuello, Luis G -- Jogini, Vishwanath -- Cortes, D Marien -- Pan, Albert C -- Gagnon, Dominique G -- Dalmas, Olivier -- Cordero-Morales, Julio F -- Chakrapani, Sudha -- Roux, Benoit -- Perozo, Eduardo -- R01 GM057846/GM/NIGMS NIH HHS/ -- R01 GM057846-15/GM/NIGMS NIH HHS/ -- R01 GM062342/GM/NIGMS NIH HHS/ -- R01 GM062342-05/GM/NIGMS NIH HHS/ -- R01-GM57846/GM/NIGMS NIH HHS/ -- R01-GM62342/GM/NIGMS NIH HHS/ -- England -- Nature. 2010 Jul 8;466(7303):272-5. doi: 10.1038/nature09136.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Molecular Biology, The University of Chicago, 929 E 57th Street, Chicago, Illinois 60637, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20613845" target="_blank"〉PubMed〈/a〉
    Keywords: Allosteric Regulation ; Bacterial Proteins/*chemistry/genetics/*metabolism ; Cysteine/genetics/metabolism ; Electron Spin Resonance Spectroscopy ; Humans ; Hydrogen Bonding ; *Ion Channel Gating ; Kinetics ; Models, Molecular ; Molecular Dynamics Simulation ; Phenylalanine/metabolism ; Potassium Channels/*chemistry/genetics/*metabolism ; Protein Conformation ; Shaker Superfamily of Potassium Channels/chemistry/genetics/metabolism ; Streptomyces lividans/*chemistry ; Structure-Activity Relationship
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 65
    facet.materialart.
    Unknown
    Type IIA topoisomerase inhibition by a new class of antibacterial agents (2010)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2010-08-06
    Description: Despite the success of genomics in identifying new essential bacterial genes, there is a lack of sustainable leads in antibacterial drug discovery to address increasing multidrug resistance. Type IIA topoisomerases cleave and religate DNA to regulate DNA topology and are a major class of antibacterial and anticancer drug targets, yet there is no well developed structural basis for understanding drug action. Here we report the 2.1 A crystal structure of a potent, new class, broad-spectrum antibacterial agent in complex with Staphylococcus aureus DNA gyrase and DNA, showing a new mode of inhibition that circumvents fluoroquinolone resistance in this clinically important drug target. The inhibitor 'bridges' the DNA and a transient non-catalytic pocket on the two-fold axis at the GyrA dimer interface, and is close to the active sites and fluoroquinolone binding sites. In the inhibitor complex the active site seems poised to cleave the DNA, with a single metal ion observed between the TOPRIM (topoisomerase/primase) domain and the scissile phosphate. This work provides new insights into the mechanism of topoisomerase action and a platform for structure-based drug design of a new class of antibacterial agents against a clinically proven, but conformationally flexible, enzyme class.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bax, Benjamin D -- Chan, Pan F -- Eggleston, Drake S -- Fosberry, Andrew -- Gentry, Daniel R -- Gorrec, Fabrice -- Giordano, Ilaria -- Hann, Michael M -- Hennessy, Alan -- Hibbs, Martin -- Huang, Jianzhong -- Jones, Emma -- Jones, Jo -- Brown, Kristin Koretke -- Lewis, Ceri J -- May, Earl W -- Saunders, Martin R -- Singh, Onkar -- Spitzfaden, Claus E -- Shen, Carol -- Shillings, Anthony -- Theobald, Andrew J -- Wohlkonig, Alexandre -- Pearson, Neil D -- Gwynn, Michael N -- Wellcome Trust/United Kingdom -- England -- Nature. 2010 Aug 19;466(7309):935-40. doi: 10.1038/nature09197. Epub 2010 Aug 4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Molecular Discovery Research, GlaxoSmithKline, Medicines Research Centre, Gunnels Wood Road, Stevenage, Hertfordshire, SG1 2NY, UK. benjamin.d.bax@gsk.com〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20686482" target="_blank"〉PubMed〈/a〉
    Keywords: Anti-Bacterial Agents/*chemistry/metabolism/*pharmacology ; Apoenzymes/chemistry/metabolism ; Arginine/metabolism ; Aspartic Acid/metabolism ; Binding Sites ; Catalytic Domain ; Ciprofloxacin/chemistry/metabolism ; Crystallography, X-Ray ; DNA/chemistry/metabolism ; DNA Cleavage ; DNA Gyrase/*chemistry/metabolism ; DNA, Superhelical/chemistry/metabolism ; Drug Design ; Drug Resistance ; Escherichia coli/enzymology ; Manganese/metabolism ; Models, Molecular ; Protein Conformation ; Quinolines/*chemistry/metabolism/*pharmacology ; Quinolones/chemistry/metabolism ; Staphylococcus aureus/*enzymology ; Structure-Activity Relationship ; *Topoisomerase II Inhibitors
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 66
    facet.materialart.
    Unknown
    Clinical efficacy of a RAF inhibitor needs broad target blockade in BRAF-mutant melanoma (2010)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2010-09-09
    Description: B-RAF is the most frequently mutated protein kinase in human cancers. The finding that oncogenic mutations in BRAF are common in melanoma, followed by the demonstration that these tumours are dependent on the RAF/MEK/ERK pathway, offered hope that inhibition of B-RAF kinase activity could benefit melanoma patients. Herein, we describe the structure-guided discovery of PLX4032 (RG7204), a potent inhibitor of oncogenic B-RAF kinase activity. Preclinical experiments demonstrated that PLX4032 selectively blocked the RAF/MEK/ERK pathway in BRAF mutant cells and caused regression of BRAF mutant xenografts. Toxicology studies confirmed a wide safety margin consistent with the high degree of selectivity, enabling Phase 1 clinical trials using a crystalline formulation of PLX4032 (ref. 5). In a subset of melanoma patients, pathway inhibition was monitored in paired biopsy specimens collected before treatment initiation and following two weeks of treatment. This analysis revealed substantial inhibition of ERK phosphorylation, yet clinical evaluation did not show tumour regressions. At higher drug exposures afforded by a new amorphous drug formulation, greater than 80% inhibition of ERK phosphorylation in the tumours of patients correlated with clinical response. Indeed, the Phase 1 clinical data revealed a remarkably high 81% response rate in metastatic melanoma patients treated at an oral dose of 960 mg twice daily. These data demonstrate that BRAF-mutant melanomas are highly dependent on B-RAF kinase activity.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2948082/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2948082/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bollag, Gideon -- Hirth, Peter -- Tsai, James -- Zhang, Jiazhong -- Ibrahim, Prabha N -- Cho, Hanna -- Spevak, Wayne -- Zhang, Chao -- Zhang, Ying -- Habets, Gaston -- Burton, Elizabeth A -- Wong, Bernice -- Tsang, Garson -- West, Brian L -- Powell, Ben -- Shellooe, Rafe -- Marimuthu, Adhirai -- Nguyen, Hoa -- Zhang, Kam Y J -- Artis, Dean R -- Schlessinger, Joseph -- Su, Fei -- Higgins, Brian -- Iyer, Raman -- D'Andrea, Kurt -- Koehler, Astrid -- Stumm, Michael -- Lin, Paul S -- Lee, Richard J -- Grippo, Joseph -- Puzanov, Igor -- Kim, Kevin B -- Ribas, Antoni -- McArthur, Grant A -- Sosman, Jeffrey A -- Chapman, Paul B -- Flaherty, Keith T -- Xu, Xiaowei -- Nathanson, Katherine L -- Nolop, Keith -- K24 CA097588/CA/NCI NIH HHS/ -- P50 CA093372/CA/NCI NIH HHS/ -- P50 CA093372-01/CA/NCI NIH HHS/ -- R01 CA118871/CA/NCI NIH HHS/ -- R01 CA118871-01A1/CA/NCI NIH HHS/ -- England -- Nature. 2010 Sep 30;467(7315):596-9. doi: 10.1038/nature09454.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Plexxikon Inc., 91 Bolivar Drive, Berkeley, California 94710, USA. gbollag@plexxikon.com〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20823850" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Animals ; Dogs ; Extracellular Signal-Regulated MAP Kinases/antagonists & inhibitors/metabolism ; Humans ; Indoles/administration & dosage/adverse effects/chemistry/*therapeutic use ; MAP Kinase Signaling System/drug effects ; Macaca fascicularis ; Melanoma/*drug therapy/*enzymology/genetics/pathology ; Models, Molecular ; Mutant Proteins/antagonists & inhibitors/chemistry/genetics/metabolism ; Mutation/*genetics ; Neoplasm Metastasis ; Phosphorylation/drug effects ; Positron-Emission Tomography ; Proto-Oncogene Proteins B-raf/*antagonists & ; inhibitors/chemistry/genetics/metabolism ; Rats ; Substrate Specificity ; Sulfonamides/administration & dosage/adverse effects/chemistry/*therapeutic use ; Xenograft Model Antitumor Assays
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 67
    facet.materialart.
    Unknown
    Anti-diabetic drugs inhibit obesity-linked phosphorylation of PPARgamma by Cdk5 (2010)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2010-07-24
    Description: Obesity induced in mice by high-fat feeding activates the protein kinase Cdk5 (cyclin-dependent kinase 5) in adipose tissues. This results in phosphorylation of the nuclear receptor PPARgamma (peroxisome proliferator-activated receptor gamma), a dominant regulator of adipogenesis and fat cell gene expression, at serine 273. This modification of PPARgamma does not alter its adipogenic capacity, but leads to dysregulation of a large number of genes whose expression is altered in obesity, including a reduction in the expression of the insulin-sensitizing adipokine, adiponectin. The phosphorylation of PPARgamma by Cdk5 is blocked by anti-diabetic PPARgamma ligands, such as rosiglitazone and MRL24. This inhibition works both in vivo and in vitro, and is completely independent of classical receptor transcriptional agonism. Similarly, inhibition of PPARgamma phosphorylation in obese patients by rosiglitazone is very tightly associated with the anti-diabetic effects of this drug. All these findings strongly suggest that Cdk5-mediated phosphorylation of PPARgamma may be involved in the pathogenesis of insulin-resistance, and present an opportunity for development of an improved generation of anti-diabetic drugs through PPARgamma.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2987584/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2987584/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Choi, Jang Hyun -- Banks, Alexander S -- Estall, Jennifer L -- Kajimura, Shingo -- Bostrom, Pontus -- Laznik, Dina -- Ruas, Jorge L -- Chalmers, Michael J -- Kamenecka, Theodore M -- Bluher, Matthias -- Griffin, Patrick R -- Spiegelman, Bruce M -- DK087853/DK/NIDDK NIH HHS/ -- DK31405/DK/NIDDK NIH HHS/ -- K99 DK087853/DK/NIDDK NIH HHS/ -- R01 GM084041/GM/NIGMS NIH HHS/ -- R01 GM084041-03/GM/NIGMS NIH HHS/ -- R01-GM084041/GM/NIGMS NIH HHS/ -- R37 DK031405/DK/NIDDK NIH HHS/ -- R37 DK031405-30/DK/NIDDK NIH HHS/ -- S10 RR027270/RR/NCRR NIH HHS/ -- U54 MH084512/MH/NIMH NIH HHS/ -- U54 MH084512-020010/MH/NIMH NIH HHS/ -- U54-MH084512/MH/NIMH NIH HHS/ -- Intramural NIH HHS/ -- England -- Nature. 2010 Jul 22;466(7305):451-6. doi: 10.1038/nature09291.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cancer Biology and Division of Metabolism and Chronic Disease, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20651683" target="_blank"〉PubMed〈/a〉
    Keywords: Adipose Tissue/drug effects/metabolism/physiopathology ; Amino Acid Sequence ; Animals ; Cell Line ; Cyclin-Dependent Kinase 5/*antagonists & inhibitors/genetics/metabolism ; Diabetes Mellitus, Experimental/complications/*drug therapy/metabolism ; Dietary Fats/pharmacology ; Humans ; Insulin/metabolism ; Ligands ; Mice ; Models, Molecular ; Obesity/chemically induced/complications/*metabolism/physiopathology ; PPAR gamma/agonists/*metabolism ; Phosphorylation/drug effects ; Phosphoserine/metabolism ; Protein Conformation ; Thiazolidinediones/*pharmacology/therapeutic use
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 68
    facet.materialart.
    Unknown
    Structural basis for 5'-nucleotide base-specific recognition of guide RNA by human AGO2 (2010)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2010-05-28
    Description: MicroRNAs (miRNAs) mediate post-transcriptional gene regulation through association with Argonaute proteins (AGOs). Crystal structures of archaeal and bacterial homologues of AGOs have shown that the MID (middle) domain mediates the interaction with the phosphorylated 5' end of the miRNA guide strand and this interaction is thought to be independent of the identity of the 5' nucleotide in these systems. However, analysis of the known sequences of eukaryotic miRNAs and co-immunoprecipitation experiments indicate that there is a clear bias for U or A at the 5' position. Here we report the crystal structure of a MID domain from a eukaryotic AGO protein, human AGO2. The structure, in complex with nucleoside monophosphates (AMP, CMP, GMP, and UMP) mimicking the 5' end of miRNAs, shows that there are specific contacts made between the base of UMP or AMP and a rigid loop in the MID domain. Notably, the structure of the loop discriminates against CMP and GMP and dissociation constants calculated from NMR titration experiments confirm these results, showing that AMP (0.26 mM) and UMP (0.12 mM) bind with up to 30-fold higher affinity than either CMP (3.6 mM) or GMP (3.3 mM). This study provides structural evidence for nucleotide-specific interactions in the MID domain of eukaryotic AGO proteins and explains the observed preference for U or A at the 5' end of miRNAs.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Frank, Filipp -- Sonenberg, Nahum -- Nagar, Bhushan -- MOP-82929/Canadian Institutes of Health Research/Canada -- England -- Nature. 2010 Jun 10;465(7299):818-22. doi: 10.1038/nature09039. Epub 2010 May 26.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, McGill University, Montreal, Quebec H3G 0B1, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20505670" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Monophosphate/metabolism ; Argonaute Proteins ; Base Sequence ; Crystallography, X-Ray ; Cytidine Monophosphate/metabolism ; Eukaryotic Initiation Factor-2/*chemistry/*metabolism ; Guanosine Monophosphate/metabolism ; Humans ; Kinetics ; Magnetic Resonance Spectroscopy ; Models, Molecular ; Protein Structure, Tertiary ; RNA, Guide/chemistry/*genetics/*metabolism ; Structure-Activity Relationship ; Substrate Specificity ; Thermodynamics ; Uridine Monophosphate/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 69
    facet.materialart.
    Unknown
    A mechanically stabilized receptor-ligand flex-bond important in the vasculature (2010)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2010-08-21
    Description: Haemostasis in the arteriolar circulation mediated by von Willebrand factor (VWF) binding to platelets is an example of an adhesive interaction that must withstand strong hydrodynamic forces acting on cells. VWF is a concatenated, multifunctional protein that has binding sites for platelets as well as subendothelial collagen. Binding of the A1 domain in VWF to the glycoprotein Ib alpha subunit (GPIbalpha) on the surface of platelets mediates crosslinking of platelets to one another and the formation of a platelet plug for arterioles. The importance of VWF is illustrated by its mutation in von Willebrand disease, a bleeding diathesis. Here, we describe a novel mechanochemical specialization of the A1-GPIbalpha bond for force-resistance. We have developed a method that enables, for the first time, repeated measurements of the binding and unbinding of a receptor and ligand in a single molecule (ReaLiSM). We demonstrate two states of the receptor-ligand bond, that is, a flex-bond. One state is seen at low force; a second state begins to engage at 10 pN with a approximately 20-fold longer lifetime and greater force resistance. The lifetimes of the two states, how force exponentiates lifetime, and the kinetics of switching between the two states are all measured. For the first time, single-molecule measurements on this system are in agreement with bulk phase measurements. The results have important implications not only for how platelets bound to VWF are able to resist force to plug arterioles, but also how increased flow activates platelet plug formation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4117310/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4117310/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kim, Jongseong -- Zhang, Cheng-Zhong -- Zhang, Xiaohui -- Springer, Timothy A -- HL-48675/HL/NHLBI NIH HHS/ -- P01 HL048675/HL/NHLBI NIH HHS/ -- England -- Nature. 2010 Aug 19;466(7309):992-5. doi: 10.1038/nature09295.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Immune Disease Institute, Children's Hospital Boston and Department of Pathology, Harvard Medical School, 3 Blackfan Circle, Boston, Massachusetts 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20725043" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Arterioles/cytology/*physiology ; Blood Coagulation/*physiology ; Blood Platelets/chemistry/cytology/*metabolism ; Cell Line ; Hemorheology ; Humans ; Kinetics ; Ligands ; Membrane Glycoproteins/chemistry/*metabolism ; Mice ; Models, Chemical ; Models, Molecular ; Platelet Glycoprotein GPIb-IX Complex ; Protein Binding ; Protein Structure, Tertiary ; Tensile Strength ; von Willebrand Factor/chemistry/*metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 70
    facet.materialart.
    Unknown
    Structure of a fucose transporter in an outward-open conformation (2010)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2010-09-30
    Description: The major facilitator superfamily (MFS) transporters are an ancient and widespread family of secondary active transporters. In Escherichia coli, the uptake of l-fucose, a source of carbon for microorganisms, is mediated by an MFS proton symporter, FucP. Despite intensive study of the MFS transporters, atomic structure information is only available on three proteins and the outward-open conformation has yet to be captured. Here we report the crystal structure of FucP at 3.1 A resolution, which shows that it contains an outward-open, amphipathic cavity. The similarly folded amino and carboxyl domains of FucP have contrasting surface features along the transport path, with negative electrostatic potential on the N domain and hydrophobic surface on the C domain. FucP only contains two acidic residues along the transport path, Asp 46 and Glu 135, which can undergo cycles of protonation and deprotonation. Their essential role in active transport is supported by both in vivo and in vitro experiments. Structure-based biochemical analyses provide insights into energy coupling, substrate recognition and the transport mechanism of FucP.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dang, Shangyu -- Sun, Linfeng -- Huang, Yongjian -- Lu, Feiran -- Liu, Yufeng -- Gong, Haipeng -- Wang, Jiawei -- Yan, Nieng -- England -- Nature. 2010 Oct 7;467(7316):734-8. doi: 10.1038/nature09406. Epub 2010 Sep 26.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉State Key Laboratory of Bio-membrane and Membrane Biotechnology, Center for Structural Biology, School of Life Sciences and School of Medicine, Tsinghua University, Beijing 100084, China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20877283" target="_blank"〉PubMed〈/a〉
    Keywords: Crystallography, X-Ray ; Escherichia coli/*chemistry ; Escherichia coli Proteins/*chemistry/metabolism ; Fucose/metabolism ; Hydrophobic and Hydrophilic Interactions ; Models, Biological ; Models, Molecular ; Monosaccharide Transport Proteins/*chemistry/metabolism ; Protein Conformation ; Protons ; Rotation ; Static Electricity ; Symporters/*chemistry/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 71
    facet.materialart.
    Unknown
    Structure and immune recognition of trimeric pre-fusion HIV-1 Env (2014)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2014-10-09
    Description: The human immunodeficiency virus type 1 (HIV-1) envelope (Env) spike, comprising three gp120 and three gp41 subunits, is a conformational machine that facilitates HIV-1 entry by rearranging from a mature unliganded state, through receptor-bound intermediates, to a post-fusion state. As the sole viral antigen on the HIV-1 virion surface, Env is both the target of neutralizing antibodies and a focus of vaccine efforts. Here we report the structure at 3.5 A resolution for an HIV-1 Env trimer captured in a mature closed state by antibodies PGT122 and 35O22. This structure reveals the pre-fusion conformation of gp41, indicates rearrangements needed for fusion activation, and defines parameters of immune evasion and immune recognition. Pre-fusion gp41 encircles amino- and carboxy-terminal strands of gp120 with four helices that form a membrane-proximal collar, fastened by insertion of a fusion peptide-proximal methionine into a gp41-tryptophan clasp. Spike rearrangements required for entry involve opening the clasp and expelling the termini. N-linked glycosylation and sequence-variable regions cover the pre-fusion closed spike; we used chronic cohorts to map the prevalence and location of effective HIV-1-neutralizing responses, which were distinguished by their recognition of N-linked glycan and tolerance for epitope-sequence variation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4348022/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4348022/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pancera, Marie -- Zhou, Tongqing -- Druz, Aliaksandr -- Georgiev, Ivelin S -- Soto, Cinque -- Gorman, Jason -- Huang, Jinghe -- Acharya, Priyamvada -- Chuang, Gwo-Yu -- Ofek, Gilad -- Stewart-Jones, Guillaume B E -- Stuckey, Jonathan -- Bailer, Robert T -- Joyce, M Gordon -- Louder, Mark K -- Tumba, Nancy -- Yang, Yongping -- Zhang, Baoshan -- Cohen, Myron S -- Haynes, Barton F -- Mascola, John R -- Morris, Lynn -- Munro, James B -- Blanchard, Scott C -- Mothes, Walther -- Connors, Mark -- Kwong, Peter D -- AI0678501/AI/NIAID NIH HHS/ -- AI100645/AI/NIAID NIH HHS/ -- P01 GM056550/GM/NIGMS NIH HHS/ -- P01-GM56550/GM/NIGMS NIH HHS/ -- P30 AI050410/AI/NIAID NIH HHS/ -- R01 GM098859/GM/NIGMS NIH HHS/ -- R01-GM098859/GM/NIGMS NIH HHS/ -- R21 AI100696/AI/NIAID NIH HHS/ -- R21-AI100696/AI/NIAID NIH HHS/ -- UL1 TR000142/TR/NCATS NIH HHS/ -- UM1 AI100645/AI/NIAID NIH HHS/ -- ZIA AI005023-13/Intramural NIH HHS/ -- ZIA AI005024-13/Intramural NIH HHS/ -- England -- Nature. 2014 Oct 23;514(7523):455-61. doi: 10.1038/nature13808. Epub 2014 Oct 8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. ; HIV-Specific Immunity Section, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. ; Center for HIV and STIs, National Institute for Communicable Diseases of the National Health Laboratory Service (NHLS), Sandringham, Johannesburg 2131, South Africa. ; Departments of Medicine, Epidemiology, Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA. ; Duke University Human Vaccine Institute, Departments of Medicine, Surgery, Pediatrics and Immunology, Duke University School of Medicine, and the Center for HIV/AIDS Vaccine Immunology-Immunogen Discovery at Duke University, Durham, North Carolina 27710, USA. ; 1] Center for HIV and STIs, National Institute for Communicable Diseases of the National Health Laboratory Service (NHLS), Sandringham, Johannesburg 2131, South Africa [2] University of the Witwatersrand, Braamfontein, Johannesburg 2000, South Africa [3] Centre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu-Natal, Durban 4041, South Africa. ; Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, Connecticut 06536, USA. ; Department of Physiology and Biophysics, Weill Cornell Medical College of Cornell University, New York, New York 10021, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25296255" target="_blank"〉PubMed〈/a〉
    Keywords: AIDS Vaccines/chemistry/immunology ; Amino Acid Sequence ; Antibodies, Neutralizing/immunology ; Cohort Studies ; Crystallography, X-Ray ; Genetic Variation ; Glycosylation ; HIV Antibodies/immunology ; HIV Envelope Protein gp120/*chemistry/genetics/*immunology ; HIV Envelope Protein gp41/*chemistry/genetics/*immunology ; HIV Infections/immunology ; Humans ; Immune Evasion ; Membrane Fusion ; Models, Molecular ; Molecular Sequence Data ; Polysaccharides/chemistry/immunology ; Protein Multimerization ; Protein Structure, Quaternary ; Protein Subunits/chemistry/genetics/immunology ; Structural Homology, Protein ; Virus Internalization
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 72
    facet.materialart.
    Unknown
    Rapid development of broadly influenza neutralizing antibodies through redundant mutations (2014)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2014-10-09
    Description: The neutralizing antibody response to influenza virus is dominated by antibodies that bind to the globular head of haemagglutinin, which undergoes a continuous antigenic drift, necessitating the re-formulation of influenza vaccines on an annual basis. Recently, several laboratories have described a new class of rare influenza-neutralizing antibodies that target a conserved site in the haemagglutinin stem. Most of these antibodies use the heavy-chain variable region VH1-69 gene, and structural data demonstrate that they bind to the haemagglutinin stem through conserved heavy-chain complementarity determining region (HCDR) residues. However, the VH1-69 antibodies are highly mutated and are produced by some but not all individuals, suggesting that several somatic mutations may be required for their development. To address this, here we characterize 197 anti-stem antibodies from a single donor, reconstruct the developmental pathways of several VH1-69 clones and identify two key elements that are required for the initial development of most VH1-69 antibodies: a polymorphic germline-encoded phenylalanine at position 54 and a conserved tyrosine at position 98 in HCDR3. Strikingly, in most cases a single proline to alanine mutation at position 52a in HCDR2 is sufficient to confer high affinity binding to the selecting H1 antigen, consistent with rapid affinity maturation. Surprisingly, additional favourable mutations continue to accumulate, increasing the breadth of reactivity and making both the initial mutations and phenylalanine at position 54 functionally redundant. These results define VH1-69 allele polymorphism, rearrangement of the VDJ gene segments and single somatic mutations as the three requirements for generating broadly neutralizing VH1-69 antibodies and reveal an unexpected redundancy in the affinity maturation process.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pappas, Leontios -- Foglierini, Mathilde -- Piccoli, Luca -- Kallewaard, Nicole L -- Turrini, Filippo -- Silacci, Chiara -- Fernandez-Rodriguez, Blanca -- Agatic, Gloria -- Giacchetto-Sasselli, Isabella -- Pellicciotta, Gabriele -- Sallusto, Federica -- Zhu, Qing -- Vicenzi, Elisa -- Corti, Davide -- Lanzavecchia, Antonio -- U19 AI-057266/AI/NIAID NIH HHS/ -- England -- Nature. 2014 Dec 18;516(7531):418-22. doi: 10.1038/nature13764. Epub 2014 Oct 5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Insitute for Research in Biomedicine, Universita della Svizzera Italiana, Via Vincenzo Vela 6, 6500 Bellinzona, Switzerland. ; Department of Infectious Diseases and Vaccines MedImmune LLC, One MedImmune Way, Gaithersburg, Maryland 20878, USA. ; Viral Pathogens and Biosafety Unit, San Raffaele Scientific Institute, Via Olgettina 58, 20132 Milan, Italy. ; Humabs BioMed SA, Via Mirasole 1, 6500 Bellinzona, Switzerland. ; Unit of Preventive Medicine, San Raffaele Scientific Institute, Via Olgettina 58, 20132 Milan, Italy. ; 1] Insitute for Research in Biomedicine, Universita della Svizzera Italiana, Via Vincenzo Vela 6, 6500 Bellinzona, Switzerland [2] Humabs BioMed SA, Via Mirasole 1, 6500 Bellinzona, Switzerland [3]. ; 1] Insitute for Research in Biomedicine, Universita della Svizzera Italiana, Via Vincenzo Vela 6, 6500 Bellinzona, Switzerland [2] Insitute for Microbiology, ETH Zurich, Wolfgang-Pauli-Strasse 10, 8093 Zurich, Switzerland [3].〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25296253" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Amino Acid Sequence ; Antibodies, Neutralizing/*genetics ; Cells, Cultured ; Complementarity Determining Regions/chemistry/*genetics ; Female ; Hemagglutinin Glycoproteins, Influenza Virus/immunology ; Humans ; Immunoglobulin Heavy Chains/genetics ; Influenza, Human/*immunology/virology ; Male ; Middle Aged ; Models, Molecular ; Mutation/*genetics ; Orthomyxoviridae/*immunology/metabolism ; Polymorphism, Genetic ; Protein Binding/genetics ; Protein Structure, Tertiary ; Young Adult
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 73
    facet.materialart.
    Unknown
    DNA repair: How to accurately bypass damage (2010)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2010-06-26
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Broyde, Suse -- Patel, Dinshaw J -- R01 CA028038/CA/NCI NIH HHS/ -- England -- Nature. 2010 Jun 24;465(7301):1023-4. doi: 10.1038/4651023a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20577203" target="_blank"〉PubMed〈/a〉
    Keywords: Biocatalysis ; Crystallography, X-Ray ; DNA/chemistry/metabolism ; *DNA Damage ; *DNA Repair ; DNA-Directed DNA Polymerase/*chemistry/genetics/*metabolism ; Humans ; Models, Molecular ; Mutation, Missense/genetics ; Pyrimidine Dimers/chemistry/*metabolism ; Saccharomyces cerevisiae/*enzymology/genetics ; Skin Neoplasms/enzymology/genetics ; Structure-Activity Relationship ; Xeroderma Pigmentosum/enzymology/genetics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 74
    facet.materialart.
    Unknown
    Molecular basis of nitrate uptake by the plant nitrate transporter NRT1.1 (2014)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2014-02-28
    Description: The NRT1/PTR family of proton-coupled transporters are responsible for nitrogen assimilation in eukaryotes and bacteria through the uptake of peptides. However, in most plant species members of this family have evolved to transport nitrate as well as additional secondary metabolites and hormones. In response to falling nitrate levels, NRT1.1 is phosphorylated on an intracellular threonine that switches the transporter from a low-affinity to high-affinity state. Here we present both the apo and nitrate-bound crystal structures of Arabidopsis thaliana NRT1.1, which together with in vitro binding and transport data identify a key role for His 356 in nitrate binding. Our data support a model whereby phosphorylation increases structural flexibility and in turn the rate of transport. Comparison with peptide transporters further reveals how the NRT1/PTR family has evolved to recognize diverse nitrogenous ligands, while maintaining elements of a conserved coupling mechanism within this superfamily of nutrient transporters.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3982047/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3982047/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Parker, Joanne L -- Newstead, Simon -- G0900399/Medical Research Council/United Kingdom -- England -- Nature. 2014 Mar 6;507(7490):68-72. doi: 10.1038/nature13116. Epub 2014 Feb 26.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UK. ; 1] Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UK [2] Research Complex at Harwell, Rutherford Appleton Laboratory, Didcot OX11 0FA, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24572366" target="_blank"〉PubMed〈/a〉
    Keywords: Anion Transport Proteins/*chemistry/*metabolism ; Arabidopsis/*chemistry/metabolism ; Crystallography, X-Ray ; Histidine/chemistry/metabolism ; Ion Transport ; Models, Molecular ; Nitrates/chemistry/*metabolism ; Phosphorylation ; Phosphothreonine/metabolism ; Plant Proteins/*chemistry/*metabolism ; Protein Conformation ; Protons ; Structure-Activity Relationship ; Substrate Specificity
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 75
    facet.materialart.
    Unknown
    The mechanism of sodium and substrate release from the binding pocket of vSGLT (2010)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2010-12-07
    Description: Membrane co-transport proteins that use a five-helix inverted repeat motif have recently emerged as one of the largest structural classes of secondary active transporters. However, despite many structural advances there is no clear evidence of how ion and substrate transport are coupled. Here we report a comprehensive study of the sodium/galactose transporter from Vibrio parahaemolyticus (vSGLT), consisting of molecular dynamics simulations, biochemical characterization and a new crystal structure of the inward-open conformation at a resolution of 2.7 A. Our data show that sodium exit causes a reorientation of transmembrane helix 1 that opens an inner gate required for substrate exit, and also triggers minor rigid-body movements in two sets of transmembrane helical bundles. This cascade of events, initiated by sodium release, ensures proper timing of ion and substrate release. Once set in motion, these molecular changes weaken substrate binding to the transporter and allow galactose readily to enter the intracellular space. Additionally, we identify an allosteric pathway between the sodium-binding sites, the unwound portion of transmembrane helix 1 and the substrate-binding site that is essential in the coupling of co-transport.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3736980/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3736980/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Watanabe, Akira -- Choe, Seungho -- Chaptal, Vincent -- Rosenberg, John M -- Wright, Ernest M -- Grabe, Michael -- Abramson, Jeff -- DK19567/DK/NIDDK NIH HHS/ -- GM078844/GM/NIGMS NIH HHS/ -- R01 DK019567/DK/NIDDK NIH HHS/ -- R01 GM078844/GM/NIGMS NIH HHS/ -- RGY0069/PHS HHS/ -- England -- Nature. 2010 Dec 16;468(7326):988-91. doi: 10.1038/nature09580. Epub 2010 Dec 5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physiology, University of California, Los Angeles, Los Angeles, California 90095-1759, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21131949" target="_blank"〉PubMed〈/a〉
    Keywords: Allosteric Regulation ; Binding Sites ; Biological Transport ; Crystallography, X-Ray ; Galactose/*metabolism ; Models, Molecular ; Molecular Dynamics Simulation ; Protein Conformation ; Sodium/*metabolism ; Symporters/*chemistry/*metabolism ; Vibrio parahaemolyticus/*chemistry
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 76
    facet.materialart.
    Unknown
    Microtubule nucleating gamma-TuSC assembles structures with 13-fold microtubule-like symmetry (2010)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2010-07-16
    Description: Microtubules are nucleated in vivo by gamma-tubulin complexes. The 300-kDa gamma-tubulin small complex (gamma-TuSC), consisting of two molecules of gamma-tubulin and one copy each of the accessory proteins Spc97 and Spc98, is the conserved, essential core of the microtubule nucleating machinery. In metazoa multiple gamma-TuSCs assemble with other proteins into gamma-tubulin ring complexes (gamma-TuRCs). The structure of gamma-TuRC indicated that it functions as a microtubule template. Because each gamma-TuSC contains two molecules of gamma-tubulin, it was assumed that the gamma-TuRC-specific proteins are required to organize gamma-TuSCs to match 13-fold microtubule symmetry. Here we show that Saccharomyces cerevisiae gamma-TuSC forms rings even in the absence of other gamma-TuRC components. The yeast adaptor protein Spc110 stabilizes the rings into extended filaments and is required for oligomer formation under physiological buffer conditions. The 8-A cryo-electron microscopic reconstruction of the filament reveals 13 gamma-tubulins per turn, matching microtubule symmetry, with plus ends exposed for interaction with microtubules, implying that one turn of the filament constitutes a microtubule template. The domain structures of Spc97 and Spc98 suggest functions for conserved sequence motifs, with implications for the gamma-TuRC-specific proteins. The gamma-TuSC filaments nucleate microtubules at a low level, and the structure provides a strong hypothesis for how nucleation is regulated, converting this less active form to a potent nucleator.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2921000/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2921000/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kollman, Justin M -- Polka, Jessica K -- Zelter, Alex -- Davis, Trisha N -- Agard, David A -- F32 GM078790-03/GM/NIGMS NIH HHS/ -- R01 GM031627/GM/NIGMS NIH HHS/ -- R01 GM031627-27/GM/NIGMS NIH HHS/ -- R01 GM040506/GM/NIGMS NIH HHS/ -- R01 GM040506-21/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2010 Aug 12;466(7308):879-82. doi: 10.1038/nature09207. Epub 2010 Jul 14.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Biophysics, Howard Hughes Medical Institute, and Keck Advanced Microscopy Center, University of California, San Francisco, San Francisco, California 94158, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20631709" target="_blank"〉PubMed〈/a〉
    Keywords: Buffers ; Cryoelectron Microscopy ; Cytoskeletal Proteins/chemistry/metabolism ; Microtubule-Associated Proteins/chemistry/metabolism ; Microtubules/*chemistry/metabolism/*ultrastructure ; Models, Biological ; Models, Molecular ; Multiprotein Complexes/chemistry/metabolism/ultrastructure ; Nuclear Proteins/chemistry/metabolism ; Saccharomyces cerevisiae/chemistry/*cytology/*ultrastructure ; Saccharomyces cerevisiae Proteins/chemistry/metabolism ; Tubulin/*chemistry/metabolism/*ultrastructure
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 77
    facet.materialart.
    Unknown
    Structure of human cytoplasmic dynein-2 primed for its power stroke (2014)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2014-12-04
    Description: Members of the dynein family, consisting of cytoplasmic and axonemal isoforms, are motors that move towards the minus ends of microtubules. Cytoplasmic dynein-1 (dynein-1) plays roles in mitosis and cellular cargo transport, and is implicated in viral infections and neurodegenerative diseases. Cytoplasmic dynein-2 (dynein-2) performs intraflagellar transport and is associated with human skeletal ciliopathies. Dyneins share a conserved motor domain that couples cycles of ATP hydrolysis with conformational changes to produce movement. Here we present the crystal structure of the human cytoplasmic dynein-2 motor bound to the ATP-hydrolysis transition state analogue ADP.vanadate. The structure reveals a closure of the motor's ring of six AAA+ domains (ATPases associated with various cellular activites: AAA1-AAA6). This induces a steric clash with the linker, the key element for the generation of movement, driving it into a conformation that is primed to produce force. Ring closure also changes the interface between the stalk and buttress coiled-coil extensions of the motor domain. This drives helix sliding in the stalk which causes the microtubule binding domain at its tip to release from the microtubule. Our structure answers the key questions of how ATP hydrolysis leads to linker remodelling and microtubule affinity regulation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4336856/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4336856/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schmidt, Helgo -- Zalyte, Ruta -- Urnavicius, Linas -- Carter, Andrew P -- 100387/Wellcome Trust/United Kingdom -- MC_UP_A025_1011/Medical Research Council/United Kingdom -- WT100387/Wellcome Trust/United Kingdom -- England -- Nature. 2015 Feb 19;518(7539):435-8. doi: 10.1038/nature14023. Epub 2014 Dec 1.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Medical Research Council Laboratory of Molecular Biology, Division of Structural Studies, Francis Crick Avenue, Cambridge CB2 0QH, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25470043" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Diphosphate/analogs & derivatives/metabolism ; Binding Sites ; Crystallography, X-Ray ; *Cytoplasm ; Cytoplasmic Dyneins/*chemistry/*metabolism ; Humans ; Hydrolysis ; Models, Molecular ; Movement ; Protein Conformation
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 78
    facet.materialart.
    Unknown
    Subnanometre-resolution electron cryomicroscopy structure of a heterodimeric ABC exporter (2014)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2014-11-05
    Description: ATP-binding cassette (ABC) transporters translocate substrates across cell membranes, using energy harnessed from ATP binding and hydrolysis at their nucleotide-binding domains. ABC exporters are present both in prokaryotes and eukaryotes, with examples implicated in multidrug resistance of pathogens and cancer cells, as well as in many human diseases. TmrAB is a heterodimeric ABC exporter from the thermophilic Gram-negative eubacterium Thermus thermophilus; it is homologous to various multidrug transporters and contains one degenerate site with a non-catalytic residue next to the Walker B motif. Here we report a subnanometre-resolution structure of detergent-solubilized TmrAB in a nucleotide-free, inward-facing conformation by single-particle electron cryomicroscopy. The reconstructions clearly resolve characteristic features of ABC transporters, including helices in the transmembrane domain and nucleotide-binding domains. A cavity in the transmembrane domain is accessible laterally from the cytoplasmic side of the membrane as well as from the cytoplasm, indicating that the transporter lies in an inward-facing open conformation. The two nucleotide-binding domains remain in contact via their carboxy-terminal helices. Furthermore, comparison between our structure and the crystal structures of other ABC transporters suggests a possible trajectory of conformational changes that involves a sliding and rotating motion between the two nucleotide-binding domains during the transition from the inward-facing to outward-facing conformations.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4372080/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4372080/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kim, JungMin -- Wu, Shenping -- Tomasiak, Thomas M -- Mergel, Claudia -- Winter, Michael B -- Stiller, Sebastian B -- Robles-Colmanares, Yaneth -- Stroud, Robert M -- Tampe, Robert -- Craik, Charles S -- Cheng, Yifan -- 1P41CA196276-01/CA/NCI NIH HHS/ -- P41 CA196276/CA/NCI NIH HHS/ -- P50 GM073210/GM/NIGMS NIH HHS/ -- P50 GM082250/GM/NIGMS NIH HHS/ -- P50GM073210/GM/NIGMS NIH HHS/ -- P50GM082250/GM/NIGMS NIH HHS/ -- R01 GM024485/GM/NIGMS NIH HHS/ -- R01 GM098672/GM/NIGMS NIH HHS/ -- R01GM098672/GM/NIGMS NIH HHS/ -- R37 GM024485/GM/NIGMS NIH HHS/ -- R37GM024485/GM/NIGMS NIH HHS/ -- S10 RR026814/RR/NCRR NIH HHS/ -- S10RR026814/RR/NCRR NIH HHS/ -- England -- Nature. 2015 Jan 15;517(7534):396-400. doi: 10.1038/nature13872. Epub 2014 Nov 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmaceutical Chemistry, University of California San Francisco, 600 16th Street, San Francisco, California 94158, USA. ; Department of Biochemistry and Biophysics, University of California San Francisco, 600 16th Street, San Francisco, California 94158, USA. ; Institute of Biochemistry, Biocenter, Goethe-University Frankfurt, Max-von-Laue-Strasse 9, D-60438 Frankfurt am Main, Germany. ; 1] Department of Pharmaceutical Chemistry, University of California San Francisco, 600 16th Street, San Francisco, California 94158, USA [2] Department of Biochemistry and Biophysics, University of California San Francisco, 600 16th Street, San Francisco, California 94158, USA. ; 1] Institute of Biochemistry, Biocenter, Goethe-University Frankfurt, Max-von-Laue-Strasse 9, D-60438 Frankfurt am Main, Germany [2] Cluster of Excellence - Macromolecular Complexes, Goethe-University Frankfurt, Max-von-Laue-Strasse 9, D-60438 Frankfurt am Main, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25363761" target="_blank"〉PubMed〈/a〉
    Keywords: ATP-Binding Cassette Transporters/*chemistry/immunology/*ultrastructure ; Antigens/chemistry/immunology ; Binding Sites ; *Cryoelectron Microscopy ; Crystallography, X-Ray ; Models, Molecular ; Nucleotides/metabolism ; Protein Multimerization ; Protein Structure, Quaternary ; Protein Structure, Tertiary ; Rotation ; Thermus thermophilus/*chemistry
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 79
    facet.materialart.
    Unknown
    Reductive dehalogenase structure suggests a mechanism for B12-dependent dehalogenation (2014)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2014-10-21
    Description: Organohalide chemistry underpins many industrial and agricultural processes, and a large proportion of environmental pollutants are organohalides. Nevertheless, organohalide chemistry is not exclusively of anthropogenic origin, with natural abiotic and biological processes contributing to the global halide cycle. Reductive dehalogenases are responsible for biological dehalogenation in organohalide respiring bacteria, with substrates including polychlorinated biphenyls or dioxins. Reductive dehalogenases form a distinct subfamily of cobalamin (B12)-dependent enzymes that are usually membrane associated and oxygen sensitive, hindering detailed studies. Here we report the characterization of a soluble, oxygen-tolerant reductive dehalogenase and, by combining structure determination with EPR (electron paramagnetic resonance) spectroscopy and simulation, show that a direct interaction between the cobalamin cobalt and the substrate halogen underpins catalysis. In contrast to the carbon-cobalt bond chemistry catalysed by the other cobalamin-dependent subfamilies, we propose that reductive dehalogenases achieve reduction of the organohalide substrate via halogen-cobalt bond formation. This presents a new model in both organohalide and cobalamin (bio)chemistry that will guide future exploitation of these enzymes in bioremediation or biocatalysis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Payne, Karl A P -- Quezada, Carolina P -- Fisher, Karl -- Dunstan, Mark S -- Collins, Fraser A -- Sjuts, Hanno -- Levy, Colin -- Hay, Sam -- Rigby, Stephen E J -- Leys, David -- BB/H021523/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- Biotechnology and Biological Sciences Research Council/United Kingdom -- England -- Nature. 2015 Jan 22;517(7535):513-6. doi: 10.1038/nature13901. Epub 2014 Oct 19.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Manchester Institute for Biotechnology, University of Manchester, 131 Princess Street, Manchester M1 7DN, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25327251" target="_blank"〉PubMed〈/a〉
    Keywords: Biocatalysis ; Cobalt/chemistry/metabolism ; Crystallography, X-Ray ; Electron Spin Resonance Spectroscopy ; *Halogenation ; Models, Molecular ; Oxidation-Reduction ; Oxidoreductases/*chemistry/*metabolism ; Oxygen/metabolism ; Phenols/chemistry/metabolism ; Phyllobacteriaceae/*enzymology ; Protein Conformation ; Solubility ; Vitamin B 12/chemistry/*metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 80
    facet.materialart.
    Unknown
    Structure of the immature HIV-1 capsid in intact virus particles at 8.8 A resolution (2014)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2014-11-05
    Description: Human immunodeficiency virus type 1 (HIV-1) assembly proceeds in two stages. First, the 55 kilodalton viral Gag polyprotein assembles into a hexameric protein lattice at the plasma membrane of the infected cell, inducing budding and release of an immature particle. Second, Gag is cleaved by the viral protease, leading to internal rearrangement of the virus into the mature, infectious form. Immature and mature HIV-1 particles are heterogeneous in size and morphology, preventing high-resolution analysis of their protein arrangement in situ by conventional structural biology methods. Here we apply cryo-electron tomography and sub-tomogram averaging methods to resolve the structure of the capsid lattice within intact immature HIV-1 particles at subnanometre resolution, allowing unambiguous positioning of all alpha-helices. The resulting model reveals tertiary and quaternary structural interactions that mediate HIV-1 assembly. Strikingly, these interactions differ from those predicted by the current model based on in vitro-assembled arrays of Gag-derived proteins from Mason-Pfizer monkey virus. To validate this difference, we solve the structure of the capsid lattice within intact immature Mason-Pfizer monkey virus particles. Comparison with the immature HIV-1 structure reveals that retroviral capsid proteins, while having conserved tertiary structures, adopt different quaternary arrangements during virus assembly. The approach demonstrated here should be applicable to determine structures of other proteins at subnanometre resolution within heterogeneous environments.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schur, Florian K M -- Hagen, Wim J H -- Rumlova, Michaela -- Ruml, Tomas -- Muller, Barbara -- Krausslich, Hans-Georg -- Briggs, John A G -- England -- Nature. 2015 Jan 22;517(7535):505-8. doi: 10.1038/nature13838. Epub 2014 Nov 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Structural and Computational Biology Unit, European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany [2] Molecular Medicine Partnership Unit, European Molecular Biology Laboratory/Universitatsklinikum Heidelberg, Heidelberg, Germany. ; Structural and Computational Biology Unit, European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany. ; 1] Institute of Organic Chemistry and Biochemistry (IOCB), Academy of Sciences of the Czech Republic, v.v.i., IOCB &Gilead Research Center, Flemingovo nam. 2, 166 10 Prague, Czech Republic [2] Department of Biotechnology, Institute of Chemical Technology, Prague, Technicka 5, 166 28, Prague, Czech Republic. ; Department of Biochemistry and Microbiology, Institute of Chemical Technology, Prague, Technicka 5, 166 28, Prague, Czech Republic. ; 1] Molecular Medicine Partnership Unit, European Molecular Biology Laboratory/Universitatsklinikum Heidelberg, Heidelberg, Germany [2] Department of Infectious Diseases, Virology, Universitatsklinikum Heidelberg, Im Neuenheimer Feld 324, 69120 Heidelberg, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25363765" target="_blank"〉PubMed〈/a〉
    Keywords: Capsid/chemistry/*ultrastructure ; Capsid Proteins/chemistry/ultrastructure ; *Cryoelectron Microscopy ; *Electron Microscope Tomography ; HEK293 Cells ; HIV-1/*chemistry/*ultrastructure ; Humans ; Mason-Pfizer monkey virus/chemistry/ultrastructure ; Models, Molecular ; Protein Conformation ; Protein Multimerization ; Virion/*chemistry/*ultrastructure ; Virus Assembly
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 81
    facet.materialart.
    Unknown
    Structural insight into autoinhibition and histone H3-induced activation of DNMT3A (2014)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2014-11-11
    Description: DNA methylation is an important epigenetic modification that is essential for various developmental processes through regulating gene expression, genomic imprinting, and epigenetic inheritance. Mammalian genomic DNA methylation is established during embryogenesis by de novo DNA methyltransferases, DNMT3A and DNMT3B, and the methylation patterns vary with developmental stages and cell types. DNA methyltransferase 3-like protein (DNMT3L) is a catalytically inactive paralogue of DNMT3 enzymes, which stimulates the enzymatic activity of Dnmt3a. Recent studies have established a connection between DNA methylation and histone modifications, and revealed a histone-guided mechanism for the establishment of DNA methylation. The ATRX-DNMT3-DNMT3L (ADD) domain of Dnmt3a recognizes unmethylated histone H3 (H3K4me0). The histone H3 tail stimulates the enzymatic activity of Dnmt3a in vitro, whereas the molecular mechanism remains elusive. Here we show that DNMT3A exists in an autoinhibitory form and that the histone H3 tail stimulates its activity in a DNMT3L-independent manner. We determine the crystal structures of DNMT3A-DNMT3L (autoinhibitory form) and DNMT3A-DNMT3L-H3 (active form) complexes at 3.82 and 2.90 A resolution, respectively. Structural and biochemical analyses indicate that the ADD domain of DNMT3A interacts with and inhibits enzymatic activity of the catalytic domain (CD) through blocking its DNA-binding affinity. Histone H3 (but not H3K4me3) disrupts ADD-CD interaction, induces a large movement of the ADD domain, and thus releases the autoinhibition of DNMT3A. The finding adds another layer of regulation of DNA methylation to ensure that the enzyme is mainly activated at proper targeting loci when unmethylated H3K4 is present, and strongly supports a negative correlation between H3K4me3 and DNA methylation across the mammalian genome. Our study provides a new insight into an unexpected autoinhibition and histone H3-induced activation of the de novo DNA methyltransferase after its initial genomic positioning.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Guo, Xue -- Wang, Ling -- Li, Jie -- Ding, Zhanyu -- Xiao, Jianxiong -- Yin, Xiaotong -- He, Shuang -- Shi, Pan -- Dong, Liping -- Li, Guohong -- Tian, Changlin -- Wang, Jiawei -- Cong, Yao -- Xu, Yanhui -- England -- Nature. 2015 Jan 29;517(7536):640-4. doi: 10.1038/nature13899. Epub 2014 Nov 10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Fudan University Shanghai Cancer Center, Institute of Biomedical Sciences, Shanghai Medical College of Fudan University, Shanghai 200032, China [2] State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai 200433, China. ; Fudan University Shanghai Cancer Center, Institute of Biomedical Sciences, Shanghai Medical College of Fudan University, Shanghai 200032, China. ; National Center for Protein Science Shanghai, State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China. ; 1] High Magnetic Field Laboratory, Chinese Academy of Sciences, Hefei 230031, China [2] National Laboratory for Physical Science at the Microscale, University of Science and Technology of China, Hefei 230026, China [3] School of Life Sciences, University of Science and Technology of China, Hefei 230026, China. ; 1] National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Science, Beijing 100101, China [2] University of Chinese Academy of Science, Beijing 100049, China. ; National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Science, Beijing 100101, China. ; State Key Laboratory of Biomembrane and Membrane Biotechnology, School of Life Sciences, Tsinghua University, Beijing 100084, China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25383530" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Catalytic Domain ; Crystallography, X-Ray ; DNA/metabolism ; DNA (Cytosine-5-)-Methyltransferase/*antagonists & ; inhibitors/*chemistry/*metabolism ; DNA Methylation ; Enzyme Activation ; Histones/*chemistry/*metabolism ; Humans ; Mice ; Models, Molecular ; Protein Structure, Tertiary ; Xenopus laevis
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 82
    facet.materialart.
    Unknown
    Structure of the F-actin-tropomyosin complex (2014)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2014-12-04
    Description: Filamentous actin (F-actin) is the major protein of muscle thin filaments, and actin microfilaments are the main component of the eukaryotic cytoskeleton. Mutations in different actin isoforms lead to early-onset autosomal dominant non-syndromic hearing loss, familial thoracic aortic aneurysms and dissections, and multiple variations of myopathies. In striated muscle fibres, the binding of myosin motors to actin filaments is mainly regulated by tropomyosin and troponin. Tropomyosin also binds to F-actin in smooth muscle and in non-muscle cells and stabilizes and regulates the filaments there in the absence of troponin. Although crystal structures for monomeric actin (G-actin) are available, a high-resolution structure of F-actin is still missing, hampering our understanding of how disease-causing mutations affect the function of thin muscle filaments and microfilaments. Here we report the three-dimensional structure of F-actin at a resolution of 3.7 A in complex with tropomyosin at a resolution of 6.5 A, determined by electron cryomicroscopy. The structure reveals that the D-loop is ordered and acts as a central region for hydrophobic and electrostatic interactions that stabilize the F-actin filament. We clearly identify map density corresponding to ADP and Mg(2+) and explain the possible effect of prominent disease-causing mutants. A comparison of F-actin with G-actin reveals the conformational changes during filament formation and identifies the D-loop as their key mediator. We also confirm that negatively charged tropomyosin interacts with a positively charged groove on F-actin. Comparison of the position of tropomyosin in F-actin-tropomyosin with its position in our previously determined F-actin-tropomyosin-myosin structure reveals a myosin-induced transition of tropomyosin. Our results allow us to understand the role of individual mutations in the genesis of actin- and tropomyosin-related diseases and will serve as a strong foundation for the targeted development of drugs.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4477711/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4477711/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉von der Ecken, Julian -- Muller, Mirco -- Lehman, William -- Manstein, Dietmar J -- Penczek, Pawel A -- Raunser, Stefan -- R01 60635/PHS HHS/ -- R01 GM060635/GM/NIGMS NIH HHS/ -- R37HL036153/HL/NHLBI NIH HHS/ -- U54 094598/PHS HHS/ -- U54 GM094598/GM/NIGMS NIH HHS/ -- England -- Nature. 2015 Mar 5;519(7541):114-7. doi: 10.1038/nature14033. Epub 2014 Dec 1.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Structural Biochemistry, Max Planck Institute of Molecular Physiology, 44227 Dortmund, Germany. ; Institute for Biophysical Chemistry, Hannover Medical School, 30625 Hannover, Germany. ; Department of Physiology and Biophysics, Boston University School of Medicine, Boston, Massachusetts 02118, USA. ; Department of Biochemistry and Molecular Biology, The University of Texas, Houston Medical School, Houston, Texas 77030, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25470062" target="_blank"〉PubMed〈/a〉
    Keywords: Actins/*chemistry/genetics/*metabolism ; Adenosine Diphosphate/metabolism ; Animals ; Cryoelectron Microscopy ; Magnesium/metabolism ; Mice ; Models, Molecular ; Mutation/genetics ; Protein Conformation ; Rabbits ; Static Electricity ; Tropomyosin/*chemistry/genetics/*metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 83
    facet.materialart.
    Unknown
    Structure and mechanism of the tRNA-dependent lantibiotic dehydratase NisB (2014)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2014-11-05
    Description: Lantibiotics are a class of peptide antibiotics that contain one or more thioether bonds. The lantibiotic nisin is an antimicrobial peptide that is widely used as a food preservative to combat food-borne pathogens. Nisin contains dehydroalanine and dehydrobutyrine residues that are formed by the dehydration of Ser/Thr by the lantibiotic dehydratase NisB (ref. 2). Recent biochemical studies revealed that NisB glutamylates Ser/Thr side chains as part of the dehydration process. However, the molecular mechanism by which NisB uses glutamate to catalyse dehydration remains unresolved. Here we show that this process involves glutamyl-tRNA(Glu) to activate Ser/Thr residues. In addition, the 2.9-A crystal structure of NisB in complex with its substrate peptide NisA reveals the presence of two separate domains that catalyse the Ser/Thr glutamylation and glutamate elimination steps. The co-crystal structure also provides insights into substrate recognition by lantibiotic dehydratases. Our findings demonstrate an unexpected role for aminoacyl-tRNA in the formation of dehydroamino acids in lantibiotics, and serve as a basis for the functional characterization of the many lantibiotic-like dehydratases involved in the biosynthesis of other classes of natural products.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4430201/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4430201/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ortega, Manuel A -- Hao, Yue -- Zhang, Qi -- Walker, Mark C -- van der Donk, Wilfred A -- Nair, Satish K -- 5T32-GM070421/GM/NIGMS NIH HHS/ -- F32 GM112284/GM/NIGMS NIH HHS/ -- R01 GM 058822/GM/NIGMS NIH HHS/ -- R01 GM058822/GM/NIGMS NIH HHS/ -- R01 GM079038/GM/NIGMS NIH HHS/ -- S10 RR027109 A/RR/NCRR NIH HHS/ -- T32 GM070421/GM/NIGMS NIH HHS/ -- England -- Nature. 2015 Jan 22;517(7535):509-12. doi: 10.1038/nature13888. Epub 2014 Oct 26.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, University of Illinois at Urbana-Champaign, 600 South Mathews Avenue, Urbana, Illinois 61801, USA. ; Department of Chemistry and Howard Hughes Medical Institute, University of Illinois at Urbana-Champaign, 600 South Mathews Avenue, Urbana, Illinois 61801, USA. ; 1] Department of Biochemistry, University of Illinois at Urbana-Champaign, 600 South Mathews Avenue, Urbana, Illinois 61801, USA [2] Department of Chemistry and Howard Hughes Medical Institute, University of Illinois at Urbana-Champaign, 600 South Mathews Avenue, Urbana, Illinois 61801, USA. ; 1] Department of Biochemistry, University of Illinois at Urbana-Champaign, 600 South Mathews Avenue, Urbana, Illinois 61801, USA [2] Center for Biophysics and Computational Biology, University of Illinois at Urbana-Champaign, 600 South Mathews Avenue, Urbana, Illinois 61801, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25363770" target="_blank"〉PubMed〈/a〉
    Keywords: Bacterial Proteins/*chemistry/classification/*metabolism ; Bacteriocins/biosynthesis/*metabolism ; Crystallography, X-Ray ; Escherichia coli/genetics ; Glutamic Acid/metabolism ; Hydro-Lyases/*chemistry/classification/*metabolism ; Lactococcus lactis/*enzymology/genetics ; Membrane Proteins/*chemistry/classification/*metabolism ; Models, Molecular ; Nisin/biosynthesis/metabolism ; Phylogeny ; Protein Structure, Tertiary ; RNA, Transfer, Glu/genetics/*metabolism ; Serine/metabolism ; Threonine/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 84
    facet.materialart.
    Unknown
    Architecture and conformational switch mechanism of the ryanodine receptor (2014)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2014-12-04
    Description: Muscle contraction is initiated by the release of calcium (Ca(2+)) from the sarcoplasmic reticulum into the cytoplasm of myocytes through ryanodine receptors (RyRs). RyRs are homotetrameric channels with a molecular mass of more than 2.2 megadaltons that are regulated by several factors, including ions, small molecules and proteins. Numerous mutations in RyRs have been associated with human diseases. The molecular mechanism underlying the complex regulation of RyRs is poorly understood. Using electron cryomicroscopy, here we determine the architecture of rabbit RyR1 at a resolution of 6.1 A. We show that the cytoplasmic moiety of RyR1 contains two large alpha-solenoid domains and several smaller domains, with folds suggestive of participation in protein-protein interactions. The transmembrane domain represents a chimaera of voltage-gated sodium and pH-activated ion channels. We identify the calcium-binding EF-hand domain and show that it functions as a conformational switch allosterically gating the channel.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Efremov, Rouslan G -- Leitner, Alexander -- Aebersold, Ruedi -- Raunser, Stefan -- England -- Nature. 2015 Jan 1;517(7532):39-43. doi: 10.1038/nature13916. Epub 2014 Dec 1.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Department of Structural Biochemistry, Max Planck Institute of Molecular Physiology, 44227 Dortmund, Germany [2] Structural Biology Research Center, Vlaams Instituut voor Biotechnologie (VIB), 1050 Brussels, Belgium [3] Structural Biology Brussels, Vrije Universiteit Brussel (VUB), 1050 Brussels, Belgium. ; Department of Biology, Institute of Molecular Systems Biology, ETH Zurich, 8093 Zurich, Switzerland. ; 1] Department of Biology, Institute of Molecular Systems Biology, ETH Zurich, 8093 Zurich, Switzerland [2] Faculty of Science, University of Zurich, 8057 Zurich, Switzerland. ; Department of Structural Biochemistry, Max Planck Institute of Molecular Physiology, 44227 Dortmund, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25470059" target="_blank"〉PubMed〈/a〉
    Keywords: Allosteric Regulation/drug effects ; Animals ; Calcium/deficiency/metabolism/pharmacology ; Cryoelectron Microscopy ; Cytoplasm/metabolism ; Hydrogen-Ion Concentration ; Inositol 1,4,5-Trisphosphate Receptors/chemistry ; Ion Channel Gating/drug effects ; Models, Molecular ; Protein Binding ; Protein Structure, Tertiary/drug effects ; Rabbits ; Ryanodine Receptor Calcium Release Channel/chemistry/*metabolism/*ultrastructure ; Tacrolimus Binding Protein 1A/chemistry/metabolism/ultrastructure
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 85
    facet.materialart.
    Unknown
    Structural biology. The flu's proton escort (2010)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2010-10-23
    Description: 〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3771513/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3771513/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fiorin, Giacomo -- Carnevale, Vincenzo -- DeGrado, William F -- R37 GM054616/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2010 Oct 22;330(6003):456-8. doi: 10.1126/science.1197748.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute for Computational Molecular Science and Department of Chemistry, Temple University, Philadelphia, PA 19122-6078, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20966238" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Electron Spin Resonance Spectroscopy ; Humans ; Influenza A virus/*chemistry/physiology ; Ion Channels/*chemistry ; Magnetic Resonance Spectroscopy ; Models, Molecular ; Protein Conformation ; Protons ; Viral Matrix Proteins/*chemistry ; Xenopus
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 86
    facet.materialart.
    Unknown
    Crystal structure of the eukaryotic ribosome (2010)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2010-11-27
    Description: Crystal structures of prokaryotic ribosomes have described in detail the universally conserved core of the translation mechanism. However, many facets of the translation process in eukaryotes are not shared with prokaryotes. The crystal structure of the yeast 80S ribosome determined at 4.15 angstrom resolution reveals the higher complexity of eukaryotic ribosomes, which are 40% larger than their bacterial counterparts. Our model shows how eukaryote-specific elements considerably expand the network of interactions within the ribosome and provides insights into eukaryote-specific features of protein synthesis. Our crystals capture the ribosome in the ratcheted state, which is essential for translocation of mRNA and transfer RNA (tRNA), and in which the small ribosomal subunit has rotated with respect to the large subunit. We describe the conformational changes in both ribosomal subunits that are involved in ratcheting and their implications in coordination between the two associated subunits and in mRNA and tRNA translocation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ben-Shem, Adam -- Jenner, Lasse -- Yusupova, Gulnara -- Yusupov, Marat -- New York, N.Y. -- Science. 2010 Nov 26;330(6008):1203-9. doi: 10.1126/science.1194294.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉IGBMC (Institut de Genetique et de Biologie Moleculaire et Cellulaire), 1 rue Laurent Fries, BP10142, Illkirch F-67400, France. adam@igbmc.fr〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21109664" target="_blank"〉PubMed〈/a〉
    Keywords: Crystallization ; Crystallography, X-Ray ; Models, Molecular ; Nucleic Acid Conformation ; Peptide Chain Initiation, Translational ; Protein Binding ; *Protein Biosynthesis ; Protein Conformation ; RNA, Fungal/analysis/chemistry/metabolism ; RNA, Messenger/analysis/chemistry/metabolism ; RNA, Ribosomal/analysis/*chemistry/metabolism ; RNA, Transfer/chemistry/metabolism ; Ribosomal Proteins/analysis/*chemistry/metabolism ; Ribosome Subunits, Large, Eukaryotic/chemistry/metabolism/ultrastructure ; Ribosome Subunits, Small, Eukaryotic/chemistry/metabolism/ultrastructure ; Ribosomes/*chemistry/metabolism/*ultrastructure ; Saccharomyces cerevisiae/chemistry/genetics/metabolism/*ultrastructure ; Saccharomyces cerevisiae Proteins/analysis/chemistry/metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 87
    facet.materialart.
    Unknown
    Structural basis for activation of class Ib ribonucleotide reductase (2010)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2010-08-07
    Description: The class Ib ribonucleotide reductase of Escherichia coli can initiate reduction of nucleotides to deoxynucleotides with either a Mn(III)2-tyrosyl radical (Y*) or a Fe(III)2-Y* cofactor in the NrdF subunit. Whereas Fe(III)2-Y* can self-assemble from Fe(II)2-NrdF and O2, activation of Mn(II)2-NrdF requires a reduced flavoprotein, NrdI, proposed to form the oxidant for cofactor assembly by reduction of O2. The crystal structures reported here of E. coli Mn(II)2-NrdF and Fe(II)2-NrdF reveal different coordination environments, suggesting distinct initial binding sites for the oxidants during cofactor activation. In the structures of Mn(II)2-NrdF in complex with reduced and oxidized NrdI, a continuous channel connects the NrdI flavin cofactor to the NrdF Mn(II)2 active site. Crystallographic detection of a putative peroxide in this channel supports the proposed mechanism of Mn(III)2-Y* cofactor assembly.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3020666/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3020666/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Boal, Amie K -- Cotruvo, Joseph A Jr -- Stubbe, JoAnne -- Rosenzweig, Amy C -- GM58518/GM/NIGMS NIH HHS/ -- GM81393/GM/NIGMS NIH HHS/ -- R01 GM058518/GM/NIGMS NIH HHS/ -- R01 GM058518-13/GM/NIGMS NIH HHS/ -- Y1-CO-1020/CO/NCI NIH HHS/ -- Y1-GM-1104/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2010 Sep 17;329(5998):1526-30. doi: 10.1126/science.1190187. Epub 2010 Aug 5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, Molecular Biology and Cell Biology, Northwestern University, Evanston, IL 60208, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20688982" target="_blank"〉PubMed〈/a〉
    Keywords: Binding Sites ; Catalytic Domain ; Coenzymes/chemistry/metabolism ; Crystallography, X-Ray ; Enzyme Activation ; Escherichia coli/*enzymology ; Escherichia coli Proteins/*chemistry/*metabolism ; Ferrous Compounds/chemistry/metabolism ; Flavin Mononucleotide/chemistry/metabolism ; Flavodoxin/*chemistry/metabolism ; Hydrogen Bonding ; Ligands ; Manganese/*chemistry/metabolism ; Models, Molecular ; Oxidants/chemistry/metabolism ; Oxidation-Reduction ; Oxygen/chemistry/metabolism ; Peroxides/chemistry/metabolism ; Protein Folding ; Protein Multimerization ; Protein Subunits/chemistry/metabolism ; Ribonucleotide Reductases/*chemistry/*metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 88
    facet.materialart.
    Unknown
    Cryo-EM model of the bullet-shaped vesicular stomatitis virus (2010)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2010-02-06
    Description: Vesicular stomatitis virus (VSV) is a bullet-shaped rhabdovirus and a model system of negative-strand RNA viruses. Through direct visualization by means of cryo-electron microscopy, we show that each virion contains two nested, left-handed helices: an outer helix of matrix protein M and an inner helix of nucleoprotein N and RNA. M has a hub domain with four contact sites that link to neighboring M and N subunits, providing rigidity by clamping adjacent turns of the nucleocapsid. Side-by-side interactions between neighboring N subunits are critical for the nucleocapsid to form a bullet shape, and structure-based mutagenesis results support this description. Together, our data suggest a mechanism of VSV assembly in which the nucleocapsid spirals from the tip to become the helical trunk, both subsequently framed and rigidified by the M layer.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2892700/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2892700/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ge, Peng -- Tsao, Jun -- Schein, Stan -- Green, Todd J -- Luo, Ming -- Zhou, Z Hong -- AI050066/AI/NIAID NIH HHS/ -- AI069015/AI/NIAID NIH HHS/ -- GM071940/GM/NIGMS NIH HHS/ -- R01 AI050066/AI/NIAID NIH HHS/ -- R01 AI050066-08/AI/NIAID NIH HHS/ -- R01 AI069015/AI/NIAID NIH HHS/ -- R01 GM071940/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2010 Feb 5;327(5966):689-93. doi: 10.1126/science.1181766.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology, Immunology, and Molecular Genetics, University of California at Los Angeles (UCLA), Los Angeles, CA 90095-7364, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20133572" target="_blank"〉PubMed〈/a〉
    Keywords: Cryoelectron Microscopy ; Crystallography, X-Ray ; Image Processing, Computer-Assisted ; Lipid Bilayers ; Models, Molecular ; Mutagenesis ; Nucleocapsid Proteins/*chemistry/genetics/ultrastructure ; Protein Conformation ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Protein Subunits/chemistry ; RNA, Viral/*chemistry/ultrastructure ; Vesiculovirus/*chemistry/physiology/*ultrastructure ; Viral Matrix Proteins/*chemistry/ultrastructure ; Virion/chemistry/ultrastructure ; Virus Assembly
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 89
    facet.materialart.
    Unknown
    How the CCA-adding enzyme selects adenine over cytosine at position 76 of tRNA (2010)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2010-11-13
    Description: CCA-adding enzymes [ATP(CTP):tRNA nucleotidyltransferases] add CCA onto the 3' end of transfer RNA (tRNA) precursors without using a nucleic acid template. Although the mechanism by which cytosine (C) is selected at position 75 of tRNA has been established, the mechanism by which adenine (A) is selected at position 76 remains elusive. Here, we report five cocrystal structures of the enzyme complexed with both a tRNA mimic and nucleoside triphosphates under catalytically active conditions. These structures suggest that adenosine 5'-monophosphate is incorporated onto the A76 position of the tRNA via a carboxylate-assisted, one-metal-ion mechanism with aspartate 110 functioning as a general base. The discrimination against incorporation of cytidine 5'-triphosphate (CTP) at position 76 arises from improper placement of the alpha phosphate of the incoming CTP, which results from the interaction of C with arginine 224 and prevents the nucleophilic attack by the 3' hydroxyl group of cytidine75.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3087442/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3087442/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pan, Baocheng -- Xiong, Yong -- Steitz, Thomas A -- GM57510/GM/NIGMS NIH HHS/ -- R01 GM057510/GM/NIGMS NIH HHS/ -- R01 GM057510-13/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2010 Nov 12;330(6006):937-40. doi: 10.1126/science.1194985.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21071662" target="_blank"〉PubMed〈/a〉
    Keywords: Adenine/chemistry/*metabolism ; Adenosine Monophosphate/metabolism ; Adenosine Triphosphate/chemistry/metabolism ; Archaeoglobus fulgidus/*enzymology ; Catalytic Domain ; Crystallization ; Crystallography, X-Ray ; Cytidine Triphosphate/metabolism ; Cytosine/chemistry/*metabolism ; Hydrogen Bonding ; Models, Molecular ; Nucleic Acid Conformation ; Protein Conformation ; Protein Structure, Tertiary ; RNA Nucleotidyltransferases/*chemistry/*metabolism ; RNA, Transfer/chemistry/*metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 90
    facet.materialart.
    Unknown
    Insight into the mechanism of the influenza A proton channel from a structure in a lipid bilayer (2010)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2010-10-23
    Description: The M2 protein from the influenza A virus, an acid-activated proton-selective channel, has been the subject of numerous conductance, structural, and computational studies. However, little is known at the atomic level about the heart of the functional mechanism for this tetrameric protein, a His(37)-Trp(41) cluster. We report the structure of the M2 conductance domain (residues 22 to 62) in a lipid bilayer, which displays the defining features of the native protein that have not been attainable from structures solubilized by detergents. We propose that the tetrameric His(37)-Trp(41) cluster guides protons through the channel by forming and breaking hydrogen bonds between adjacent pairs of histidines and through specific interactions of the histidines with the tryptophan gate. This mechanism explains the main observations on M2 proton conductance.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3384994/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3384994/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sharma, Mukesh -- Yi, Myunggi -- Dong, Hao -- Qin, Huajun -- Peterson, Emily -- Busath, David D -- Zhou, Huan-Xiang -- Cross, Timothy A -- AI023007/AI/NIAID NIH HHS/ -- R01 AI023007/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2010 Oct 22;330(6003):509-12. doi: 10.1126/science.1191750.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry and Biochemistry, Florida State University, Tallahassee, FL 32306, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20966252" target="_blank"〉PubMed〈/a〉
    Keywords: Histidine/chemistry ; Hydrogen Bonding ; Hydrogen-Ion Concentration ; Influenza A virus/*chemistry/physiology ; Ion Channels/*chemistry ; Ion Transport ; Lipid Bilayers ; Models, Molecular ; Nuclear Magnetic Resonance, Biomolecular ; Protein Conformation ; Protein Structure, Tertiary ; *Protons ; Tryptophan/chemistry ; Viral Matrix Proteins/*chemistry
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 91
    facet.materialart.
    Unknown
    The structure of cbb3 cytochrome oxidase provides insights into proton pumping (2010)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2010-06-26
    Description: The heme-copper oxidases (HCOs) accomplish the key event of aerobic respiration; they couple O2 reduction and transmembrane proton pumping. To gain new insights into the still enigmatic process, we structurally characterized a C-family HCO--essential for the pathogenicity of many bacteria--that differs from the two other HCO families, A and B, that have been structurally analyzed. The x-ray structure of the C-family cbb3 oxidase from Pseudomonas stutzeri at 3.2 angstrom resolution shows an electron supply system different from families A and B. Like family-B HCOs, C HCOs have only one pathway, which conducts protons via an alternative tyrosine-histidine cross-link. Structural differences around hemes b and b3 suggest a different redox-driven proton-pumping mechanism and provide clues to explain the higher activity of family-C HCOs at low oxygen concentrations.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Buschmann, Sabine -- Warkentin, Eberhard -- Xie, Hao -- Langer, Julian D -- Ermler, Ulrich -- Michel, Hartmut -- New York, N.Y. -- Science. 2010 Jul 16;329(5989):327-30. doi: 10.1126/science.1187303. Epub 2010 Jun 24.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Max-Planck-Institut fur Biophysik, Max-von-Laue-Strasse 3, D-60438 Frankfurt/Main, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20576851" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Catalytic Domain ; Crystallography, X-Ray ; Cytoplasm/metabolism ; Electron Transport ; Electron Transport Complex IV/*chemistry/*metabolism ; Heme/chemistry ; Histidine/chemistry ; Hydrogen Bonding ; Models, Molecular ; Molecular Sequence Data ; Oxidation-Reduction ; Oxygen/metabolism ; Periplasm/metabolism ; Protein Conformation ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Proton Pumps/*chemistry/*metabolism ; *Protons ; Pseudomonas stutzeri/*enzymology ; Tyrosine/chemistry
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 92
    facet.materialart.
    Unknown
    FCHo proteins are nucleators of clathrin-mediated endocytosis (2010)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2010-05-08
    Description: Clathrin-mediated endocytosis, the major pathway for ligand internalization into eukaryotic cells, is thought to be initiated by the clustering of clathrin and adaptors around receptors destined for internalization. However, here we report that the membrane-sculpting F-BAR domain-containing Fer/Cip4 homology domain-only proteins 1 and 2 (FCHo1/2) were required for plasma membrane clathrin-coated vesicle (CCV) budding and marked sites of CCV formation. Changes in FCHo1/2 expression levels correlated directly with numbers of CCV budding events, ligand endocytosis, and synaptic vesicle marker recycling. FCHo1/2 proteins bound specifically to the plasma membrane and recruited the scaffold proteins eps15 and intersectin, which in turn engaged the adaptor complex AP2. The FCHo F-BAR membrane-bending activity was required, leading to the proposal that FCHo1/2 sculpt the initial bud site and recruit the clathrin machinery for CCV formation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2883440/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2883440/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Henne, William Mike -- Boucrot, Emmanuel -- Meinecke, Michael -- Evergren, Emma -- Vallis, Yvonne -- Mittal, Rohit -- McMahon, Harvey T -- MC_U105178795/Medical Research Council/United Kingdom -- U.1051.02.007(78795)/Medical Research Council/United Kingdom -- Medical Research Council/United Kingdom -- New York, N.Y. -- Science. 2010 Jun 4;328(5983):1281-4. doi: 10.1126/science.1188462. Epub 2010 May 6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Medical Research Council, Laboratory of Molecular Biology (MRC-LMB), Hills Road, Cambridge CB2 0QH, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20448150" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptor Protein Complex 2/metabolism ; Adaptor Proteins, Signal Transducing ; Adaptor Proteins, Vesicular Transport/metabolism ; Animals ; Calcium-Binding Proteins/metabolism ; Cell Line ; Cell Membrane/metabolism ; Cells, Cultured ; Clathrin/*metabolism ; Clathrin-Coated Vesicles/*metabolism ; *Endocytosis ; HeLa Cells ; Humans ; Intracellular Signaling Peptides and Proteins/metabolism ; Membrane Proteins ; Mice ; Models, Molecular ; Neurons/cytology/metabolism ; Phosphoproteins/metabolism ; Protein Multimerization ; Protein Structure, Tertiary ; Proteins/chemistry/*metabolism ; RNA Interference ; Rats ; Rats, Sprague-Dawley ; Recombinant Fusion Proteins/metabolism ; Synaptic Vesicles/metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 93
    facet.materialart.
    Unknown
    Vibrio cholerae VpsT regulates matrix production and motility by directly sensing cyclic di-GMP (2010)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2010-02-13
    Description: Microorganisms can switch from a planktonic, free-swimming life-style to a sessile, colonial state, called a biofilm, which confers resistance to environmental stress. Conversion between the motile and biofilm life-styles has been attributed to increased levels of the prokaryotic second messenger cyclic di-guanosine monophosphate (c-di-GMP), yet the signaling mechanisms mediating such a global switch are poorly understood. Here we show that the transcriptional regulator VpsT from Vibrio cholerae directly senses c-di-GMP to inversely control extracellular matrix production and motility, which identifies VpsT as a master regulator for biofilm formation. Rather than being regulated by phosphorylation, VpsT undergoes a change in oligomerization on c-di-GMP binding.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2828054/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2828054/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Krasteva, Petya V -- Fong, Jiunn C N -- Shikuma, Nicholas J -- Beyhan, Sinem -- Navarro, Marcos V A S -- Yildiz, Fitnat H -- Sondermann, Holger -- 1R01GM081373/GM/NIGMS NIH HHS/ -- P30 EB009998/EB/NIBIB NIH HHS/ -- R01 AI055987/AI/NIAID NIH HHS/ -- R01 AI055987-06A1/AI/NIAID NIH HHS/ -- R01 GM081373/GM/NIGMS NIH HHS/ -- R01 GM081373-03/GM/NIGMS NIH HHS/ -- R01AI055987/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2010 Feb 12;327(5967):866-8. doi: 10.1126/science.1181185.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Medicine, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20150502" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Motifs ; Bacterial Proteins/chemistry/genetics/*metabolism ; Binding Sites ; Biofilms/*growth & development ; Crystallography, X-Ray ; Cyclic GMP/*analogs & derivatives/metabolism ; DNA, Bacterial/metabolism ; Dimerization ; Extracellular Matrix/*metabolism ; Gene Expression Profiling ; Gene Expression Regulation, Bacterial ; Models, Molecular ; Movement ; Point Mutation ; Polysaccharides, Bacterial/genetics/metabolism ; Protein Folding ; Protein Multimerization ; Protein Structure, Tertiary ; Signal Transduction ; Transcription Factors/chemistry/genetics/*metabolism ; Transcription, Genetic ; Vibrio cholerae O1/cytology/genetics/*physiology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 94
    facet.materialart.
    Unknown
    Genetics. First-class control of HIV-1 (2010)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2010-12-15
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉McMichael, Andrew J -- Jones, E Yvonne -- G0900084/Medical Research Council/United Kingdom -- MC_U137884177/Medical Research Council/United Kingdom -- New York, N.Y. -- Science. 2010 Dec 10;330(6010):1488-90. doi: 10.1126/science.1200035.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford OS3 9DS, UK. andrew.mcmichael@ndm.ox.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21148380" target="_blank"〉PubMed〈/a〉
    Keywords: Acquired Immunodeficiency Syndrome/genetics/immunology/physiopathology ; Amino Acid Motifs ; Disease Progression ; *Genes, MHC Class I ; Genome-Wide Association Study ; HIV Infections/*genetics/*immunology/physiopathology ; HIV Long-Term Survivors ; *HIV-1/immunology ; HLA-B Antigens/chemistry/*genetics/immunology/metabolism ; HLA-B14 Antigen ; HLA-B27 Antigen/chemistry/genetics/immunology/metabolism ; Humans ; Killer Cells, Natural/immunology ; Models, Molecular ; Polymorphism, Single Nucleotide ; Protein Conformation
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 95
    facet.materialart.
    Unknown
    Molecular basis of alternating access membrane transport by the sodium-hydantoin transporter Mhp1 (2010)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2010-04-24
    Description: The structure of the sodium-benzylhydantoin transport protein Mhp1 from Microbacterium liquefaciens comprises a five-helix inverted repeat, which is widespread among secondary transporters. Here, we report the crystal structure of an inward-facing conformation of Mhp1 at 3.8 angstroms resolution, complementing its previously described structures in outward-facing and occluded states. From analyses of the three structures and molecular dynamics simulations, we propose a mechanism for the transport cycle in Mhp1. Switching from the outward- to the inward-facing state, to effect the inward release of sodium and benzylhydantoin, is primarily achieved by a rigid body movement of transmembrane helices 3, 4, 8, and 9 relative to the rest of the protein. This forms the basis of an alternating access mechanism applicable to many transporters of this emerging superfamily.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2885435/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2885435/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shimamura, Tatsuro -- Weyand, Simone -- Beckstein, Oliver -- Rutherford, Nicholas G -- Hadden, Jonathan M -- Sharples, David -- Sansom, Mark S P -- Iwata, So -- Henderson, Peter J F -- Cameron, Alexander D -- 062164/Z/00/Z/Wellcome Trust/United Kingdom -- 079209/Wellcome Trust/United Kingdom -- BB/C51725/Biotechnology and Biological Sciences Research Council/United Kingdom -- BB/G020043/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- BB/G023425/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- BBS/B/14418/Biotechnology and Biological Sciences Research Council/United Kingdom -- New York, N.Y. -- Science. 2010 Apr 23;328(5977):470-3. doi: 10.1126/science.1186303.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Molecular Biosciences, Membrane Protein Crystallography Group, Imperial College, London SW7 2AZ, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20413494" target="_blank"〉PubMed〈/a〉
    Keywords: Actinomycetales/*chemistry/metabolism ; Amino Acid Motifs ; Bacterial Proteins/chemistry/metabolism ; Binding Sites ; Biological Transport ; Crystallography, X-Ray ; Hydantoins/chemistry/*metabolism ; Ion Transport ; Membrane Transport Proteins/*chemistry/*metabolism ; Models, Molecular ; Molecular Dynamics Simulation ; Protein Conformation ; Protein Folding ; Protein Structure, Secondary ; Sodium/*metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 96
    facet.materialart.
    Unknown
    Biochemistry. An ensemble view of allostery (2010)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2010-02-06
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hilser, Vincent J -- GM63747/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2010 Feb 5;327(5966):653-4. doi: 10.1126/science.1186121.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Molecular Biology, and Sealy Center for Structural Biology and Molecular Biophysics, University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA. vjhilser@utmb.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20133562" target="_blank"〉PubMed〈/a〉
    Keywords: *Allosteric Regulation ; Allosteric Site ; Ligands ; Models, Biological ; Models, Molecular ; Molecular Motor Proteins/chemistry/metabolism ; Protein Conformation ; Protein Subunits/*chemistry/*metabolism ; Proteins/*chemistry/*metabolism ; *Signal Transduction
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 97
    facet.materialart.
    Unknown
    Computational design of an enzyme catalyst for a stereoselective bimolecular Diels-Alder reaction (2010)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2010-07-22
    Description: The Diels-Alder reaction is a cornerstone in organic synthesis, forming two carbon-carbon bonds and up to four new stereogenic centers in one step. No naturally occurring enzymes have been shown to catalyze bimolecular Diels-Alder reactions. We describe the de novo computational design and experimental characterization of enzymes catalyzing a bimolecular Diels-Alder reaction with high stereoselectivity and substrate specificity. X-ray crystallography confirms that the structure matches the design for the most active of the enzymes, and binding site substitutions reprogram the substrate specificity. Designed stereoselective catalysts for carbon-carbon bond-forming reactions should be broadly useful in synthetic chemistry.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3241958/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3241958/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Siegel, Justin B -- Zanghellini, Alexandre -- Lovick, Helena M -- Kiss, Gert -- Lambert, Abigail R -- St Clair, Jennifer L -- Gallaher, Jasmine L -- Hilvert, Donald -- Gelb, Michael H -- Stoddard, Barry L -- Houk, Kendall N -- Michael, Forrest E -- Baker, David -- R01 GM075962/GM/NIGMS NIH HHS/ -- T32 GM008268/GM/NIGMS NIH HHS/ -- T32 GM008268-24/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2010 Jul 16;329(5989):309-13. doi: 10.1126/science.1190239.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20647463" target="_blank"〉PubMed〈/a〉
    Keywords: Acrylamides/chemistry ; Algorithms ; Butadienes/chemistry ; Carbon/*chemistry ; Catalysis ; Catalytic Domain ; Computer Simulation ; *Computer-Aided Design ; Crystallography, X-Ray ; Enzymes/*chemistry/genetics ; Hydrogen Bonding ; Hydrophobic and Hydrophilic Interactions ; Kinetics ; Models, Molecular ; Mutagenesis ; Physicochemical Processes ; Protein Conformation ; *Protein Engineering ; Proteins/*chemistry/genetics ; Software ; Stereoisomerism ; Substrate Specificity
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 98
    facet.materialart.
    Unknown
    Multiple functional groups of varying ratios in metal-organic frameworks (2010)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2010-02-13
    Description: We show that metal-organic frameworks (MOFs) can incorporate a large number of different functionalities on linking groups in a way that mixes the linker, rather than forming separate domains. We made complex MOFs from 1,4-benzenedicarboxylate (denoted by "A" in this work) and its derivatives -NH2, -Br, -(Cl)2, -NO2, -(CH3)2, -C4H4, -(OC3H5)2, and -(OC7H7)2 (denoted by "B" to "I," respectively) to synthesize 18 multivariate (MTV) MOF-5 type structures that contain up to eight distinct functionalities in one phase. The backbone (zinc oxide and phenylene units) of these structures is ordered, but the distribution of functional groups is disordered. The complex arrangements of several functional groups within the pores can lead to properties that are not simply linear sums of those of the pure components. For example, a member of this series, MTV-MOF-5-EHI, exhibits up to 400% better selectivity for carbon dioxide over carbon monoxide compared with its best same-link counterparts.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Deng, Hexiang -- Doonan, Christian J -- Furukawa, Hiroyasu -- Ferreira, Ricardo B -- Towne, John -- Knobler, Carolyn B -- Wang, Bo -- Yaghi, Omar M -- New York, N.Y. -- Science. 2010 Feb 12;327(5967):846-50. doi: 10.1126/science.1181761.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉California Nanosystems Institute, University of California-Los Angeles (UCLA)-Department of Energy (DOE) Institute of Genomics and Proteomics, Department of Chemistry and Biochemistry, UCLA, 607 Charles E. Young Drive East, Los Angeles, CA 90095, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20150497" target="_blank"〉PubMed〈/a〉
    Keywords: Carbon Dioxide/chemistry ; Carbon Monoxide/chemistry ; Chemical Phenomena ; Crystallization ; Crystallography, X-Ray ; Magnetic Resonance Spectroscopy ; Metals/*chemistry ; Models, Chemical ; Models, Molecular ; Molecular Structure ; Phthalic Acids/*chemistry ; Zinc Oxide/*chemistry
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 99
    facet.materialart.
    Unknown
    Self-assembly of Janus dendrimers into uniform dendrimersomes and other complex architectures (2010)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2010-05-22
    Description: Self-assembled nanostructures obtained from natural and synthetic amphiphiles serve as mimics of biological membranes and enable the delivery of drugs, proteins, genes, and imaging agents. Yet the precise molecular arrangements demanded by these functions are difficult to achieve. Libraries of amphiphilic Janus dendrimers, prepared by facile coupling of tailored hydrophilic and hydrophobic branched segments, have been screened by cryogenic transmission electron microscopy, revealing a rich palette of morphologies in water, including vesicles, denoted dendrimersomes, cubosomes, disks, tubular vesicles, and helical ribbons. Dendrimersomes marry the stability and mechanical strength obtainable from polymersomes with the biological function of stabilized phospholipid liposomes, plus superior uniformity of size, ease of formation, and chemical functionalization. This modular synthesis strategy provides access to systematic tuning of molecular structure and of self-assembled architecture.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Percec, Virgil -- Wilson, Daniela A -- Leowanawat, Pawaret -- Wilson, Christopher J -- Hughes, Andrew D -- Kaucher, Mark S -- Hammer, Daniel A -- Levine, Dalia H -- Kim, Anthony J -- Bates, Frank S -- Davis, Kevin P -- Lodge, Timothy P -- Klein, Michael L -- DeVane, Russell H -- Aqad, Emad -- Rosen, Brad M -- Argintaru, Andreea O -- Sienkowska, Monika J -- Rissanen, Kari -- Nummelin, Sami -- Ropponen, Jarmo -- New York, N.Y. -- Science. 2010 May 21;328(5981):1009-14. doi: 10.1126/science.1185547.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, Philadelphia, PA 19104-6323, USA. percec@sas.upenn.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20489021" target="_blank"〉PubMed〈/a〉
    Keywords: Antibiotics, Antineoplastic/administration & dosage ; Biomimetic Materials/chemistry ; Cryoelectron Microscopy ; Dendrimers/*chemistry ; Doxorubicin/administration & dosage ; Drug Carriers ; Hydrophobic and Hydrophilic Interactions ; *Membranes, Artificial ; Models, Molecular ; Molecular Dynamics Simulation ; Molecular Structure ; *Nanostructures ; Surface Properties ; Surface-Active Agents/chemistry ; Water
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 100
    facet.materialart.
    Unknown
    The major genetic determinants of HIV-1 control affect HLA class I peptide presentation (2010)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2010-11-06
    Description: Infectious and inflammatory diseases have repeatedly shown strong genetic associations within the major histocompatibility complex (MHC); however, the basis for these associations remains elusive. To define host genetic effects on the outcome of a chronic viral infection, we performed genome-wide association analysis in a multiethnic cohort of HIV-1 controllers and progressors, and we analyzed the effects of individual amino acids within the classical human leukocyte antigen (HLA) proteins. We identified 〉300 genome-wide significant single-nucleotide polymorphisms (SNPs) within the MHC and none elsewhere. Specific amino acids in the HLA-B peptide binding groove, as well as an independent HLA-C effect, explain the SNP associations and reconcile both protective and risk HLA alleles. These results implicate the nature of the HLA-viral peptide interaction as the major factor modulating durable control of HIV infection.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3235490/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3235490/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉International HIV Controllers Study -- Pereyra, Florencia -- Jia, Xiaoming -- McLaren, Paul J -- Telenti, Amalio -- de Bakker, Paul I W -- Walker, Bruce D -- Ripke, Stephan -- Brumme, Chanson J -- Pulit, Sara L -- Carrington, Mary -- Kadie, Carl M -- Carlson, Jonathan M -- Heckerman, David -- Graham, Robert R -- Plenge, Robert M -- Deeks, Steven G -- Gianniny, Lauren -- Crawford, Gabriel -- Sullivan, Jordan -- Gonzalez, Elena -- Davies, Leela -- Camargo, Amy -- Moore, Jamie M -- Beattie, Nicole -- Gupta, Supriya -- Crenshaw, Andrew -- Burtt, Noel P -- Guiducci, Candace -- Gupta, Namrata -- Gao, Xiaojiang -- Qi, Ying -- Yuki, Yuko -- Piechocka-Trocha, Alicja -- Cutrell, Emily -- Rosenberg, Rachel -- Moss, Kristin L -- Lemay, Paul -- O'Leary, Jessica -- Schaefer, Todd -- Verma, Pranshu -- Toth, Ildiko -- Block, Brian -- Baker, Brett -- Rothchild, Alissa -- Lian, Jeffrey -- Proudfoot, Jacqueline -- Alvino, Donna Marie L -- Vine, Seanna -- Addo, Marylyn M -- Allen, Todd M -- Altfeld, Marcus -- Henn, Matthew R -- Le Gall, Sylvie -- Streeck, Hendrik -- Haas, David W -- Kuritzkes, Daniel R -- Robbins, Gregory K -- Shafer, Robert W -- Gulick, Roy M -- Shikuma, Cecilia M -- Haubrich, Richard -- Riddler, Sharon -- Sax, Paul E -- Daar, Eric S -- Ribaudo, Heather J -- Agan, Brian -- Agarwal, Shanu -- Ahern, Richard L -- Allen, Brady L -- Altidor, Sherly -- Altschuler, Eric L -- Ambardar, Sujata -- Anastos, Kathryn -- Anderson, Ben -- Anderson, Val -- Andrady, Ushan -- Antoniskis, Diana -- Bangsberg, David -- Barbaro, Daniel -- Barrie, William -- Bartczak, J -- Barton, Simon -- Basden, Patricia -- Basgoz, Nesli -- Bazner, Suzane -- Bellos, Nicholaos C -- Benson, Anne M -- Berger, Judith -- Bernard, Nicole F -- Bernard, Annette M -- Birch, Christopher -- Bodner, Stanley J -- Bolan, Robert K -- Boudreaux, Emilie T -- Bradley, Meg -- Braun, James F -- Brndjar, Jon E -- Brown, Stephen J -- Brown, Katherine -- Brown, Sheldon T -- Burack, Jedidiah -- Bush, Larry M -- Cafaro, Virginia -- Campbell, Omobolaji -- Campbell, John -- Carlson, Robert H -- Carmichael, J Kevin -- Casey, Kathleen K -- Cavacuiti, Chris -- Celestin, Gregory -- Chambers, Steven T -- Chez, Nancy -- Chirch, Lisa M -- Cimoch, Paul J -- Cohen, Daniel -- Cohn, Lillian E -- Conway, Brian -- Cooper, David A -- Cornelson, Brian -- Cox, David T -- Cristofano, Michael V -- Cuchural, George Jr -- Czartoski, Julie L -- Dahman, Joseph M -- Daly, Jennifer S -- Davis, Benjamin T -- Davis, Kristine -- Davod, Sheila M -- DeJesus, Edwin -- Dietz, Craig A -- Dunham, Eleanor -- Dunn, Michael E -- Ellerin, Todd B -- Eron, Joseph J -- Fangman, John J W -- Farel, Claire E -- Ferlazzo, Helen -- Fidler, Sarah -- Fleenor-Ford, Anita -- Frankel, Renee -- Freedberg, Kenneth A -- French, Neel K -- Fuchs, Jonathan D -- Fuller, Jon D -- Gaberman, Jonna -- Gallant, Joel E -- Gandhi, Rajesh T -- Garcia, Efrain -- Garmon, Donald -- Gathe, Joseph C Jr -- Gaultier, Cyril R -- Gebre, Wondwoosen -- Gilman, Frank D -- Gilson, Ian -- Goepfert, Paul A -- Gottlieb, Michael S -- Goulston, Claudia -- Groger, Richard K -- Gurley, T Douglas -- Haber, Stuart -- Hardwicke, Robin -- Hardy, W David -- Harrigan, P Richard -- Hawkins, Trevor N -- Heath, Sonya -- Hecht, Frederick M -- Henry, W Keith -- Hladek, Melissa -- Hoffman, Robert P -- Horton, James M -- Hsu, Ricky K -- Huhn, Gregory D -- Hunt, Peter -- Hupert, Mark J -- Illeman, Mark L -- Jaeger, Hans -- Jellinger, Robert M -- John, Mina -- Johnson, Jennifer A -- Johnson, Kristin L -- Johnson, Heather -- Johnson, Kay -- Joly, Jennifer -- Jordan, Wilbert C -- Kauffman, Carol A -- Khanlou, Homayoon -- Killian, Robert K -- Kim, Arthur Y -- Kim, David D -- Kinder, Clifford A -- Kirchner, Jeffrey T -- Kogelman, Laura -- Kojic, Erna Milunka -- Korthuis, P Todd -- Kurisu, Wayne -- Kwon, Douglas S -- LaMar, Melissa -- Lampiris, Harry -- Lanzafame, Massimiliano -- Lederman, Michael M -- Lee, David M -- Lee, Jean M L -- Lee, Marah J -- Lee, Edward T Y -- Lemoine, Janice -- Levy, Jay A -- Llibre, Josep M -- Liguori, Michael A -- Little, Susan J -- Liu, Anne Y -- Lopez, Alvaro J -- Loutfy, Mono R -- Loy, Dawn -- Mohammed, Debbie Y -- Man, Alan -- Mansour, Michael K -- Marconi, Vincent C -- Markowitz, Martin -- Marques, Rui -- Martin, Jeffrey N -- Martin, Harold L Jr -- Mayer, Kenneth Hugh -- McElrath, M Juliana -- McGhee, Theresa A -- McGovern, Barbara H -- McGowan, Katherine -- McIntyre, Dawn -- Mcleod, Gavin X -- Menezes, Prema -- Mesa, Greg -- Metroka, Craig E -- Meyer-Olson, Dirk -- Miller, Andy O -- Montgomery, Kate -- Mounzer, Karam C -- Nagami, Ellen H -- Nagin, Iris -- Nahass, Ronald G -- Nelson, Margret O -- Nielsen, Craig -- Norene, David L -- O'Connor, David H -- Ojikutu, Bisola O -- Okulicz, Jason -- Oladehin, Olakunle O -- Oldfield, Edward C 3rd -- Olender, Susan A -- Ostrowski, Mario -- Owen, William F Jr -- Pae, Eunice -- Parsonnet, Jeffrey -- Pavlatos, Andrew M -- Perlmutter, Aaron M -- Pierce, Michael N -- Pincus, Jonathan M -- Pisani, Leandro -- Price, Lawrence Jay -- Proia, Laurie -- Prokesch, Richard C -- Pujet, Heather Calderon -- Ramgopal, Moti -- Rathod, Almas -- Rausch, Michael -- Ravishankar, J -- Rhame, Frank S -- Richards, Constance Shamuyarira -- Richman, Douglas D -- Rodes, Berta -- Rodriguez, Milagros -- Rose, Richard C 3rd -- Rosenberg, Eric S -- Rosenthal, Daniel -- Ross, Polly E -- Rubin, David S -- Rumbaugh, Elease -- Saenz, Luis -- Salvaggio, Michelle R -- Sanchez, William C -- Sanjana, Veeraf M -- Santiago, Steven -- Schmidt, Wolfgang -- Schuitemaker, Hanneke -- Sestak, Philip M -- Shalit, Peter -- Shay, William -- Shirvani, Vivian N -- Silebi, Vanessa I -- Sizemore, James M Jr -- Skolnik, Paul R -- Sokol-Anderson, Marcia -- Sosman, James M -- Stabile, Paul -- Stapleton, Jack T -- Starrett, Sheree -- Stein, Francine -- Stellbrink, Hans-Jurgen -- Sterman, F Lisa -- Stone, Valerie E -- Stone, David R -- Tambussi, Giuseppe -- Taplitz, Randy A -- Tedaldi, Ellen M -- Theisen, William -- Torres, Richard -- Tosiello, Lorraine -- Tremblay, Cecile -- Tribble, Marc A -- Trinh, Phuong D -- Tsao, Alice -- Ueda, Peggy -- Vaccaro, Anthony -- Valadas, Emilia -- Vanig, Thanes J -- Vecino, Isabel -- Vega, Vilma M -- Veikley, Wenoah -- Wade, Barbara H -- Walworth, Charles -- Wanidworanun, Chingchai -- Ward, Douglas J -- Warner, Daniel A -- Weber, Robert D -- Webster, Duncan -- Weis, Steve -- Wheeler, David A -- White, David J -- Wilkins, Ed -- Winston, Alan -- Wlodaver, Clifford G -- van't Wout, Angelique -- Wright, David P -- Yang, Otto O -- Yurdin, David L -- Zabukovic, Brandon W -- Zachary, Kimon C -- Zeeman, Beth -- Zhao, Meng -- AI030914/AI/NIAID NIH HHS/ -- AI068636/AI/NIAID NIH HHS/ -- AI069415/AI/NIAID NIH HHS/ -- AI069419/AI/NIAID NIH HHS/ -- AI069423/AI/NIAID NIH HHS/ -- AI069424/AI/NIAID NIH HHS/ -- AI069428/AI/NIAID NIH HHS/ -- AI069432/AI/NIAID NIH HHS/ -- AI069434/AI/NIAID NIH HHS/ -- AI069450/AI/NIAID NIH HHS/ -- AI069452/AI/NIAID NIH HHS/ -- AI069465/AI/NIAID NIH HHS/ -- AI069471/AI/NIAID NIH HHS/ -- AI069472/AI/NIAID NIH HHS/ -- AI069474/AI/NIAID NIH HHS/ -- AI069477/AI/NIAID NIH HHS/ -- AI069484/AI/NIAID NIH HHS/ -- AI069495/AI/NIAID NIH HHS/ -- AI069501/AI/NIAID NIH HHS/ -- AI069502/AI/NIAID NIH HHS/ -- AI069511/AI/NIAID NIH HHS/ -- AI069513/AI/NIAID NIH HHS/ -- AI069532/AI/NIAID NIH HHS/ -- AI069556/AI/NIAID NIH HHS/ -- AI077505/AI/NIAID NIH HHS/ -- AI087145/AI/NIAID NIH HHS/ -- AI25859/AI/NIAID NIH HHS/ -- AI27661/AI/NIAID NIH HHS/ -- AI28568/AI/NIAID NIH HHS/ -- AI30914/AI/NIAID NIH HHS/ -- AI34835/AI/NIAID NIH HHS/ -- AI34853/AI/NIAID NIH HHS/ -- AI38844/AI/NIAID NIH HHS/ -- AI46370/AI/NIAID NIH HHS/ -- AI68634/AI/NIAID NIH HHS/ -- AI69467/AI/NIAID NIH HHS/ -- AL32782/PHS HHS/ -- HHSN261200800001E/PHS HHS/ -- K23 DA019809/DA/NIDA NIH HHS/ -- K24 AI051966/AI/NIAID NIH HHS/ -- K24 AI064086/AI/NIAID NIH HHS/ -- K24 AI064086-05/AI/NIAID NIH HHS/ -- K24 AI069994/AI/NIAID NIH HHS/ -- K24 AI069994-04/AI/NIAID NIH HHS/ -- K24 AI069994-05/AI/NIAID NIH HHS/ -- K24AI069994/AI/NIAID NIH HHS/ -- KL2 RR024977/RR/NCRR NIH HHS/ -- MH071205/MH/NIMH NIH HHS/ -- MH085520/MH/NIMH NIH HHS/ -- P-30 AI27763/AI/NIAID NIH HHS/ -- P-30-AI060354/AI/NIAID NIH HHS/ -- P30 AI027763/AI/NIAID NIH HHS/ -- P30 AI027763-19/AI/NIAID NIH HHS/ -- P30 AI027763-20/AI/NIAID NIH HHS/ -- P30 AI050410/AI/NIAID NIH HHS/ -- P30 AI060354/AI/NIAID NIH HHS/ -- P30 AI060354-08/AI/NIAID NIH HHS/ -- P30 AI060354-09/AI/NIAID NIH HHS/ -- R01 AI028568/AI/NIAID NIH HHS/ -- R01 AI028568-18/AI/NIAID NIH HHS/ -- R01 AI028568-19/AI/NIAID NIH HHS/ -- R01 AI028568-20/AI/NIAID NIH HHS/ -- R01 AI030914/AI/NIAID NIH HHS/ -- R01 AI030914-16/AI/NIAID NIH HHS/ -- R01 AI030914-17/AI/NIAID NIH HHS/ -- R01 AI077505/AI/NIAID NIH HHS/ -- R01 AI077505-04/AI/NIAID NIH HHS/ -- R01 AI077505-05/AI/NIAID NIH HHS/ -- R01 AI087145/AI/NIAID NIH HHS/ -- R01 AI087145-01/AI/NIAID NIH HHS/ -- R01 AI087145-02/AI/NIAID NIH HHS/ -- R01 MH054907/MH/NIMH NIH HHS/ -- R01 MH071205/MH/NIMH NIH HHS/ -- R01 MH071205-04/MH/NIMH NIH HHS/ -- R01 MH071205-05/MH/NIMH NIH HHS/ -- R24 AI067039/AI/NIAID NIH HHS/ -- R24 AI067039-06/AI/NIAID NIH HHS/ -- R24 AI067039-07/AI/NIAID NIH HHS/ -- R37 AI028568/AI/NIAID NIH HHS/ -- R37 AI028568-15/AI/NIAID NIH HHS/ -- RR024975/RR/NCRR NIH HHS/ -- T32 AI007061/AI/NIAID NIH HHS/ -- TL1 RR024978/RR/NCRR NIH HHS/ -- U01 AI027661-18/AI/NIAID NIH HHS/ -- U01 AI027661-19/AI/NIAID NIH HHS/ -- U01 AI032782-13/AI/NIAID NIH HHS/ -- U01 AI034835-07/AI/NIAID NIH HHS/ -- U01 AI034835-07S3/AI/NIAID NIH HHS/ -- U01 AI034853/AI/NIAID NIH HHS/ -- U01 AI034853-11/AI/NIAID NIH HHS/ -- U01 AI034853-12/AI/NIAID NIH HHS/ -- U01 AI038844-04/AI/NIAID NIH HHS/ -- U01 AI038844-04S1/AI/NIAID NIH HHS/ -- U01 AI038844-04S2/AI/NIAID NIH HHS/ -- U01 AI038844-04S3/AI/NIAID NIH HHS/ -- U01 AI046370-04/AI/NIAID NIH HHS/ -- U01 AI046370-05/AI/NIAID NIH HHS/ -- U01 AI069419/AI/NIAID NIH HHS/ -- U01 AI069419-05/AI/NIAID NIH HHS/ -- U01 AI069419-06/AI/NIAID NIH HHS/ -- U01 AI069423/AI/NIAID NIH HHS/ -- U01 AI069423-05/AI/NIAID NIH HHS/ -- U01 AI069423-06/AI/NIAID NIH HHS/ -- U01 AI069424/AI/NIAID NIH HHS/ -- U01 AI069424-05/AI/NIAID NIH HHS/ -- U01 AI069424-06/AI/NIAID NIH HHS/ -- U01 AI069428/AI/NIAID NIH HHS/ -- U01 AI069428-05/AI/NIAID NIH HHS/ -- U01 AI069428-06/AI/NIAID NIH HHS/ -- U01 AI069432/AI/NIAID NIH HHS/ -- U01 AI069432-05/AI/NIAID NIH HHS/ -- U01 AI069432-06/AI/NIAID NIH HHS/ -- U01 AI069434/AI/NIAID NIH HHS/ -- U01 AI069434-05/AI/NIAID NIH HHS/ -- U01 AI069434-06/AI/NIAID NIH HHS/ -- U01 AI069450/AI/NIAID NIH HHS/ -- U01 AI069450-05/AI/NIAID NIH HHS/ -- U01 AI069450-06/AI/NIAID NIH HHS/ -- U01 AI069452/AI/NIAID NIH HHS/ -- U01 AI069452-05/AI/NIAID NIH HHS/ -- U01 AI069452-06/AI/NIAID NIH HHS/ -- U01 AI069465/AI/NIAID NIH HHS/ -- U01 AI069465-05/AI/NIAID NIH HHS/ -- U01 AI069465-06/AI/NIAID NIH HHS/ -- U01 AI069467/AI/NIAID NIH HHS/ -- U01 AI069467-05/AI/NIAID NIH HHS/ -- U01 AI069467-06/AI/NIAID NIH HHS/ -- U01 AI069471/AI/NIAID NIH HHS/ -- U01 AI069471-05/AI/NIAID NIH HHS/ -- U01 AI069471-06/AI/NIAID NIH HHS/ -- U01 AI069472/AI/NIAID NIH HHS/ -- U01 AI069472-05/AI/NIAID NIH HHS/ -- U01 AI069472-06/AI/NIAID NIH HHS/ -- U01 AI069474/AI/NIAID NIH HHS/ -- U01 AI069474-05/AI/NIAID NIH HHS/ -- U01 AI069474-06/AI/NIAID NIH HHS/ -- U01 AI069477/AI/NIAID NIH HHS/ -- U01 AI069477-05/AI/NIAID NIH HHS/ -- U01 AI069477-06/AI/NIAID NIH HHS/ -- U01 AI069484/AI/NIAID NIH HHS/ -- U01 AI069484-05/AI/NIAID NIH HHS/ -- U01 AI069484-06/AI/NIAID NIH HHS/ -- U01 AI069495/AI/NIAID NIH HHS/ -- U01 AI069495-05/AI/NIAID NIH HHS/ -- U01 AI069495-06/AI/NIAID NIH HHS/ -- U01 AI069501/AI/NIAID NIH HHS/ -- U01 AI069501-05/AI/NIAID NIH HHS/ -- U01 AI069501-06/AI/NIAID NIH HHS/ -- U01 AI069502/AI/NIAID NIH HHS/ -- U01 AI069502-05/AI/NIAID NIH HHS/ -- U01 AI069502-06/AI/NIAID NIH HHS/ -- U01 AI069511/AI/NIAID NIH HHS/ -- U01 AI069511-05/AI/NIAID NIH HHS/ -- U01 AI069511-06/AI/NIAID NIH HHS/ -- U01 AI069513-05/AI/NIAID NIH HHS/ -- U01 AI069513-06/AI/NIAID NIH HHS/ -- U01 AI069532/AI/NIAID NIH HHS/ -- U01 AI069532-05/AI/NIAID NIH HHS/ -- U01 AI069532-06/AI/NIAID NIH HHS/ -- U01 AI069556-05/AI/NIAID NIH HHS/ -- U01 AI069556-06/AI/NIAID NIH HHS/ -- U01 MH085520/MH/NIMH NIH HHS/ -- U01 MH085520-01/MH/NIMH NIH HHS/ -- UL1 RR024131/RR/NCRR NIH HHS/ -- UL1 RR024131-06/RR/NCRR NIH HHS/ -- UL1 RR024131-07/RR/NCRR NIH HHS/ -- UL1 RR024975/RR/NCRR NIH HHS/ -- UL1 RR024975-04/RR/NCRR NIH HHS/ -- UL1 RR024975-05/RR/NCRR NIH HHS/ -- UM1 AI068634/AI/NIAID NIH HHS/ -- UM1 AI068634-06/AI/NIAID NIH HHS/ -- UM1 AI068634-07/AI/NIAID NIH HHS/ -- UM1 AI068636-06/AI/NIAID NIH HHS/ -- UM1 AI068636-07/AI/NIAID NIH HHS/ -- UM1 AI069477/AI/NIAID NIH HHS/ -- Howard Hughes Medical Institute/ -- Intramural NIH HHS/ -- New York, N.Y. -- Science. 2010 Dec 10;330(6010):1551-7. doi: 10.1126/science.1195271. Epub 2010 Nov 4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology (MIT) and Harvard, Boston, MA, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21051598" target="_blank"〉PubMed〈/a〉
    Keywords: African Americans/genetics ; Alleles ; Amino Acids/physiology ; *Antigen Presentation ; CD8-Positive T-Lymphocytes/immunology ; Cohort Studies ; Disease Progression ; European Continental Ancestry Group/genetics ; *Genes, MHC Class I ; Genome-Wide Association Study ; HIV Antigens/immunology ; HIV Infections/ethnology/*genetics/*immunology/virology ; HIV Long-Term Survivors ; *HIV-1/immunology ; HLA-A Antigens/chemistry/genetics/immunology/metabolism ; HLA-B Antigens/chemistry/*genetics/immunology/metabolism ; HLA-C Antigens/chemistry/genetics/immunology/metabolism ; Haplotypes ; Hispanic Americans/genetics ; Humans ; Immunity, Innate ; Logistic Models ; Models, Molecular ; Polymorphism, Single Nucleotide ; Protein Conformation ; Viral Load
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...