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
  • Chemical Engineering  (17,982)
  • Protein Conformation
  • 1
    facet.materialart.
    Unknown
    Feature Papers in Eng 2022 (2023)
    MDPI - Multidisciplinary Digital Publishing Institute
    Details
    Publication Date: 2023-06-23
    Description: The aim of this second Eng Special Issue is to collect experimental and theoretical re-search relating to engineering science and technology. The general topics of Eng are as follows: electrical, electronic and information engineering; chemical and materials engineering; energy engineering; mechanical and automotive engineering; industrial and manufacturing engineering; civil and structural engineering; aerospace engineering; biomedical engineering; geotechnical engineering and engineering geology; and ocean and environmental engineering. Therefore, the following editorial is a selection of representative works of these topics.
    Keywords: &nbsp ; Environment Management ; Environmental Engineering ; Chemical Engineering ; Materials Engineering&nbsp ; bic Book Industry Communication::T Technology, engineering, agriculture::TB Technology: general issues ; bic Book Industry Communication::T Technology, engineering, agriculture::TB Technology: general issues::TBX History of engineering & technology
    Language: English
    Format: image/jpeg
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    E-BOOK
  • 2
    facet.materialart.
    Unknown
    Integrated Chemical Processes in Liquid Multiphase Systems (2022)
    De Gruyter | De Gruyter
    Details
    Publication Date: 2024-04-05
    Description: The essential principles of green chemistry are the use of renewable raw materials, highly efficient catalysts and green solvents linked with energy efficiency and process optimization in real-time. Experts from different fields show, how to examine all levels from the molecular elementary steps up to the design and operation of an entire plant for developing novel and efficient production processes.
    Keywords: Process Engineering ; Chemical Engineering ; Technical Chemistry ; thema EDItEUR::P Mathematics and Science::PN Chemistry ; thema EDItEUR::R Earth Sciences, Geography, Environment, Planning::RN The environment ; thema EDItEUR::R Earth Sciences, Geography, Environment, Planning::RN The environment::RNU Sustainability ; thema EDItEUR::T Technology, Engineering, Agriculture, Industrial processes::TD Industrial chemistry and manufacturing technologies::TDC Industrial chemistry and chemical engineering ; thema EDItEUR::T Technology, Engineering, Agriculture, Industrial processes::TG Mechanical engineering and materials::TGM Materials science ; thema EDItEUR::T Technology, Engineering, Agriculture, Industrial processes::TQ Environmental science, engineering and technology
    Language: English
    Format: image/jpeg
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    E-BOOK
  • 3
    facet.materialart.
    Unknown
    Function and Flexibility: Friend or Foe? (2021)
    Frontiers Media SA
    Details
    Publication Date: 2023-12-20
    Description: Louis Sullivan (1856 - 1924) revolutionized architecture by designing the first skyscraper and he became famous by proclaiming that “form follows function”. When x-ray crystallographers visualized the structures of proteins for the first time, the structural biology field embraced the view that “function follows form” as the 3D-architecture of proteins could unveil various aspects of their function. Despite the original “1 gene - 1 protein structure - 1 function” relationship, nowadays a far more complicated picture emerges where the flexibility and dynamics of a protein can play a central role in a multitude of functions. The ultimate form(s) that a protein adopt when interacting with (a) partner molecule(s) are the most biologically relevant and in this context Sullivan’s quote is still appropriate: the conformation that the protein adopts follows from the function of that protein. Despite the fact that many well-characterized proteins have a well-folded structure, there is a growing interest in the conformational flexibility within proteins. This flexibility is also a balanced phenomenon: excess of flexibility can be detrimental for protein behaviour, as well as the lack thereof. Notwithstanding its importance, studying intrinsically disordered protein regions or conformational rearrangements can be a very challenging. Therefore, flexibility can be perceived as a friend or a foe, depending on the context. This e-book showcases the impact of the study of protein flexibility on the structural biology field and presents protein flexibility in the context of disease as well as its benign aspects. As detailed knowledge of the structural aspects of polypeptides remains essential to comprehend protein function, one of the future challenges for structural biology also lies with large macromolecular protein complexes. Also there the dynamics and flexibility are essential for proper functioning and molecular movement, which is an important aspect of living matter. This challenge stimulated the development of advanced techniques to study protein flexibility and the use of those techniques to address fundamental biological and biomedical problems. Those innovations should help us to unravel the intimate link between protein function and flexibility and explore new horizons.
    Keywords: Q1-390 ; conformational selection and induced fit ; protein structure ; conformational ensemble ; Protein function ; protein dynamics ; Protein Conformation ; protein flexibility ; Protein Disorder ; intrinsically disordered proteins ; Structural transition ; bic Book Industry Communication::G Reference, information & interdisciplinary subjects::GP Research & information: general
    Language: English
    Format: image/jpeg
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    E-BOOK
  • 4
    facet.materialart.
    Unknown
    Conformational photoswitching of a synthetic peptide foldamer bound within a phospholipid bilayer (2016)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2016-04-02
    Description: The dynamic properties of foldamers, synthetic molecules that mimic folded biomolecules, have mainly been explored in free solution. We report on the design, synthesis, and conformational behavior of photoresponsive foldamers bound in a phospholipid bilayer akin to a biological membrane phase. These molecules contain a chromophore, which can be switched between two configurations by different wavelengths of light, attached to a helical synthetic peptide that both promotes membrane insertion and communicates conformational change along its length. Light-induced structural changes in the chromophore are translated into global conformational changes, which are detected by monitoring the solid-state (19)F nuclear magnetic resonance signals of a remote fluorine-containing residue located 1 to 2 nanometers away. The behavior of the foldamers in the membrane phase is similar to that of analogous compounds in organic solvents.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉De Poli, Matteo -- Zawodny, Wojciech -- Quinonero, Ophelie -- Lorch, Mark -- Webb, Simon J -- Clayden, Jonathan -- New York, N.Y. -- Science. 2016 Apr 29;352(6285):575-80. doi: 10.1126/science.aad8352. Epub 2016 Mar 31.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉School of Chemistry, University of Manchester, Manchester M13 9PL, UK. ; Department of Chemistry, University of Hull, Hull HU6 7RX, UK. ; School of Chemistry, University of Manchester, Manchester M13 9PL, UK. Manchester Institute of Biotechnology, University of Manchester, Manchester M1 7DN, UK. ; School of Chemistry, University of Bristol, Bristol BS8 1TS, UK. j.clayden@bristol.ac.uk.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27033546" target="_blank"〉PubMed〈/a〉
    Keywords: Light ; Lipid Bilayers/*chemistry ; Magnetic Resonance Spectroscopy ; Peptides/*chemistry/radiation effects ; Phosphatidylcholines/*chemistry/radiation effects ; Phospholipids/*chemistry/radiation effects ; Photochemical Processes ; Protein Conformation ; Protein Folding
    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
  • 5
    facet.materialart.
    Unknown
    Structural and molecular basis for Ebola virus neutralization by protective human antibodies (2016)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2016-02-27
    Description: Ebola virus causes hemorrhagic fever with a high case fatality rate for which there is no approved therapy. Two human monoclonal antibodies, mAb100 and mAb114, in combination, protect nonhuman primates against all signs of Ebola virus disease, including viremia. Here, we demonstrate that mAb100 recognizes the base of the Ebola virus glycoprotein (GP) trimer, occludes access to the cathepsin-cleavage loop, and prevents the proteolytic cleavage of GP that is required for virus entry. We show that mAb114 interacts with the glycan cap and inner chalice of GP, remains associated after proteolytic removal of the glycan cap, and inhibits binding of cleaved GP to its receptor. These results define the basis of neutralization for two protective antibodies and may facilitate development of therapies and vaccines.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Misasi, John -- Gilman, Morgan S A -- Kanekiyo, Masaru -- Gui, Miao -- Cagigi, Alberto -- Mulangu, Sabue -- Corti, Davide -- Ledgerwood, Julie E -- Lanzavecchia, Antonio -- Cunningham, James -- Muyembe-Tamfun, Jean Jacques -- Baxa, Ulrich -- Graham, Barney S -- Xiang, Ye -- Sullivan, Nancy J -- McLellan, Jason S -- 5K08AI079381/AI/NIAID NIH HHS/ -- HHSN261200800001E/PHS HHS/ -- T32GM008704/GM/NIGMS NIH HHS/ -- Intramural NIH HHS/ -- New York, N.Y. -- Science. 2016 Mar 18;351(6279):1343-6. doi: 10.1126/science.aad6117. Epub 2016 Feb 25.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. Division of Infectious Diseases, Boston Children's Hospital, Boston, MA 02215, USA. ; Department of Biochemistry, Geisel School of Medicine at Dartmouth, Hanover, NH 03755, USA. ; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. ; Centre for Infectious Diseases Research, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Beijing Advanced Innovation Center for Structural Biology, Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing 100084 China. ; Institute for Research in Biomedicine, Universita della Svizzera Italiana, CH-6500 Bellinzona, Switzerland. ; Institute for Research in Biomedicine, Universita della Svizzera Italiana, CH-6500 Bellinzona, Switzerland. Institute of Microbiology, ETH Zurich, CH-8093 Zurich, Switzerland. ; Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. ; National Institute for Biomedical Research, National Laboratory of Public Health, Kinshasa B.P. 1197, Democratic Republic of the Congo. ; Electron Microscopy Laboratory, Cancer Research Technology Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA. ; Centre for Infectious Diseases Research, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Beijing Advanced Innovation Center for Structural Biology, Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing 100084 China. njsull@mail.nih.gov yxiang@mail.tsinghua.edu.cn. ; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. njsull@mail.nih.gov yxiang@mail.tsinghua.edu.cn.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26917592" target="_blank"〉PubMed〈/a〉
    Keywords: Antibodies, Monoclonal/*chemistry/immunology ; Antibodies, Neutralizing/*chemistry/immunology ; Antibodies, Viral/*chemistry/immunology ; Cathepsins/chemistry ; Cryoelectron Microscopy ; Crystallography, X-Ray ; Ebolavirus/*immunology ; Hemorrhagic Fever, Ebola/immunology/*prevention & control ; Humans ; Protein Conformation ; Proteolysis ; Viral Envelope Proteins/chemistry/*immunology
    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
  • 6
    facet.materialart.
    Unknown
    Structural basis of lipoprotein signal peptidase II action and inhibition by the antibiotic globomycin (2016)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2016-02-26
    Description: With functions that range from cell envelope structure to signal transduction and transport, lipoproteins constitute 2 to 3% of bacterial genomes and play critical roles in bacterial physiology, pathogenicity, and antibiotic resistance. Lipoproteins are synthesized with a signal peptide securing them to the cytoplasmic membrane with the lipoprotein domain in the periplasm or outside the cell. Posttranslational processing requires a signal peptidase II (LspA) that removes the signal peptide. Here, we report the crystal structure of LspA from Pseudomonas aeruginosa complexed with the antimicrobial globomycin at 2.8 angstrom resolution. Mutagenesis studies identify LspA as an aspartyl peptidase. In an example of molecular mimicry, globomycin appears to inhibit by acting as a noncleavable peptide that sterically blocks the active site. This structure should inform rational antibiotic drug discovery.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Vogeley, Lutz -- El Arnaout, Toufic -- Bailey, Jonathan -- Stansfeld, Phillip J -- Boland, Coilin -- Caffrey, Martin -- BB/I019855/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- New York, N.Y. -- Science. 2016 Feb 19;351(6275):876-80. doi: 10.1126/science.aad3747.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉School of Medicine and School of Biochemistry and Immunology, Trinity College Dublin, Dublin, Ireland. ; Department of Biochemistry, University of Oxford, South Parks Road, Oxford, UK. ; School of Medicine and School of Biochemistry and Immunology, Trinity College Dublin, Dublin, Ireland. martin.caffrey@tcd.ie.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26912896" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Anti-Bacterial Agents/*chemistry/pharmacology ; Aspartic Acid Endopeptidases/*antagonists & inhibitors/*chemistry/genetics ; Bacterial Proteins/*antagonists & inhibitors/*chemistry/genetics ; Catalytic Domain ; Conserved Sequence ; Crystallography, X-Ray ; Mutagenesis ; Peptides/*chemistry/pharmacology ; Protein Conformation ; Protein Processing, Post-Translational ; Pseudomonas aeruginosa/*enzymology ; 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
  • 7
    facet.materialart.
    Unknown
    The 3.8 A structure of the U4/U6.U5 tri-snRNP: Insights into spliceosome assembly and catalysis (2016)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2016-01-09
    Description: Splicing of precursor messenger RNA is accomplished by a dynamic megacomplex known as the spliceosome. Assembly of a functional spliceosome requires a preassembled U4/U6.U5 tri-snRNP complex, which comprises the U5 small nuclear ribonucleoprotein (snRNP), the U4 and U6 small nuclear RNA (snRNA) duplex, and a number of protein factors. Here we report the three-dimensional structure of a Saccharomyces cerevisiae U4/U6.U5 tri-snRNP at an overall resolution of 3.8 angstroms by single-particle electron cryomicroscopy. The local resolution for the core regions of the tri-snRNP reaches 3.0 to 3.5 angstroms, allowing construction of a refined atomic model. Our structure contains U5 snRNA, the extensively base-paired U4/U6 snRNA, and 30 proteins including Prp8 and Snu114, which amount to 8495 amino acids and 263 nucleotides with a combined molecular mass of ~1 megadalton. The catalytic nucleotide U80 from U6 snRNA exists in an inactive conformation, stabilized by its base-pairing interactions with U4 snRNA and protected by Prp3. Pre-messenger RNA is bound in the tri-snRNP through base-pairing interactions with U6 snRNA and loop I of U5 snRNA. This structure, together with that of the spliceosome, reveals the molecular choreography of the snRNAs in the activation process of the spliceosomal ribozyme.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wan, Ruixue -- Yan, Chuangye -- Bai, Rui -- Wang, Lin -- Huang, Min -- Wong, Catherine C L -- Shi, Yigong -- New York, N.Y. -- Science. 2016 Jan 29;351(6272):466-75. doi: 10.1126/science.aad6466. Epub 2016 Jan 7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Ministry of Education Key Laboratory of Protein Science, Tsinghua-Peking Joint Center for Life Sciences, Beijing Advanced Innovation Center for Structural Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China. ; National Center for Protein Science Shanghai, Institute of Biochemistry and Cell Biology, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26743623" target="_blank"〉PubMed〈/a〉
    Keywords: Catalysis ; Cryoelectron Microscopy ; Nucleic Acid Conformation ; Protein Conformation ; RNA Precursors/chemistry ; *RNA Splicing ; RNA, Messenger/chemistry ; RNA, Small Nuclear/*chemistry/ultrastructure ; Ribonucleoprotein, U4-U6 Small Nuclear/*chemistry/ultrastructure ; Ribonucleoprotein, U5 Small Nuclear/*chemistry/ultrastructure ; Saccharomyces cerevisiae/*metabolism ; Saccharomyces cerevisiae Proteins/*chemistry/ultrastructure ; Spliceosomes/*chemistry/ultrastructure
    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
  • 8
    facet.materialart.
    Unknown
    Molecular architecture of the human U4/U6.U5 tri-snRNP (2016)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2016-02-26
    Description: The U4/U6.U5 triple small nuclear ribonucleoprotein (tri-snRNP) is a major spliceosome building block. We obtained a three-dimensional structure of the 1.8-megadalton human tri-snRNP at a resolution of 7 angstroms using single-particle cryo-electron microscopy (cryo-EM). We fit all known high-resolution structures of tri-snRNP components into the EM density map and validated them by protein cross-linking. Our model reveals how the spatial organization of Brr2 RNA helicase prevents premature U4/U6 RNA unwinding in isolated human tri-snRNPs and how the ubiquitin C-terminal hydrolase-like protein Sad1 likely tethers the helicase Brr2 to its preactivation position. Comparison of our model with cryo-EM three-dimensional structures of the Saccharomyces cerevisiae tri-snRNP and Schizosaccharomyces pombe spliceosome indicates that Brr2 undergoes a marked conformational change during spliceosome activation, and that the scaffolding protein Prp8 is also rearranged to accommodate the spliceosome's catalytic RNA network.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Agafonov, Dmitry E -- Kastner, Berthold -- Dybkov, Olexandr -- Hofele, Romina V -- Liu, Wen-Ti -- Urlaub, Henning -- Luhrmann, Reinhard -- Stark, Holger -- New York, N.Y. -- Science. 2016 Mar 25;351(6280):1416-20. doi: 10.1126/science.aad2085. Epub 2016 Feb 18.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cellular Biochemistry, Max Planck Institute for Biophysical Chemistry, D-37077 Gottingen, Germany. ; Bioanalytical Mass Spectrometry, Max Planck Institute for Biophysical Chemistry, D-37077 Gottingen, Germany. Bioanalytics Group, Institute for Clinical Chemistry, University Medical Center Gottingen, D-37075 Gottingen, Germany. ; Department of 3D Electron Cryomicroscopy, Georg-August Universitat Gottingen, D-37077 Gottingen, Germany. Department of Structural Dynamics, Max Planck Institute for Biophysical Chemistry, D-37077 Gottingen, Germany. ; Bioanalytical Mass Spectrometry, Max Planck Institute for Biophysical Chemistry, D-37077 Gottingen, Germany. Bioanalytics Group, Institute for Clinical Chemistry, University Medical Center Gottingen, D-37075 Gottingen, Germany. reinhard.luehrmann@mpi-bpc.mpg.de hstark1@gwdg.de henning.urlaub@mpibpc.mpg.de. ; Department of Cellular Biochemistry, Max Planck Institute for Biophysical Chemistry, D-37077 Gottingen, Germany. reinhard.luehrmann@mpi-bpc.mpg.de hstark1@gwdg.de henning.urlaub@mpibpc.mpg.de. ; Department of 3D Electron Cryomicroscopy, Georg-August Universitat Gottingen, D-37077 Gottingen, Germany. Department of Structural Dynamics, Max Planck Institute for Biophysical Chemistry, D-37077 Gottingen, Germany. reinhard.luehrmann@mpi-bpc.mpg.de hstark1@gwdg.de henning.urlaub@mpibpc.mpg.de.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26912367" target="_blank"〉PubMed〈/a〉
    Keywords: Cryoelectron Microscopy ; Crystallography, X-Ray ; DEAD-box RNA Helicases/chemistry ; Enzyme Activation ; HeLa Cells ; Humans ; Models, Molecular ; Peptide Elongation Factors/chemistry ; Protein Conformation ; RNA Helicases/chemistry ; RNA-Binding Proteins/chemistry ; Ribonucleoprotein, U4-U6 Small Nuclear/*chemistry ; Ribonucleoprotein, U5 Small Nuclear/*chemistry ; Ribonucleoproteins, Small Nuclear/chemistry ; Saccharomyces cerevisiae Proteins/chemistry ; Schizosaccharomyces/metabolism ; Ubiquitin Thiolesterase/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
  • 9
    facet.materialart.
    Unknown
    Designer protein delivery: From natural to engineered affinity-controlled release systems (2016)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2016-03-19
    Description: Exploiting binding affinities between molecules is an established practice in many fields, including biochemical separations, diagnostics, and drug development; however, using these affinities to control biomolecule release is a more recent strategy. Affinity-controlled release takes advantage of the reversible nature of noncovalent interactions between a therapeutic protein and a binding partner to slow the diffusive release of the protein from a vehicle. This process, in contrast to degradation-controlled sustained-release formulations such as poly(lactic-co-glycolic acid) microspheres, is controlled through the strength of the binding interaction, the binding kinetics, and the concentration of binding partners. In the context of affinity-controlled release--and specifically the discovery or design of binding partners--we review advances in in vitro selection and directed evolution of proteins, peptides, and oligonucleotides (aptamers), aided by computational design.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pakulska, Malgosia M -- Miersch, Shane -- Shoichet, Molly S -- Canadian Institutes of Health Research/Canada -- New York, N.Y. -- Science. 2016 Mar 18;351(6279):aac4750. doi: 10.1126/science.aac4750.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemical Engineering and Applied Chemistry, Institute of Biomaterials and Biomedical Engineering, and Donnelly Centre, University of Toronto, Toronto, Ontario, Canada. ; Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada. ; Department of Chemical Engineering and Applied Chemistry, Institute of Biomaterials and Biomedical Engineering, and Donnelly Centre, University of Toronto, Toronto, Ontario, Canada. Department of Chemistry, University of Toronto, Toronto, Ontario, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26989257" target="_blank"〉PubMed〈/a〉
    Keywords: Chemical Engineering ; Combinatorial Chemistry Techniques ; Delayed-Action Preparations/*chemistry ; Directed Molecular Evolution ; *Drug Design ; Humans ; Lactic Acid/*chemistry ; Microspheres ; Polyglycolic Acid/*chemistry ; Proteins/*administration & dosage
    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
  • 10
    facet.materialart.
    Unknown
    Structures of a CRISPR-Cas9 R-loop complex primed for DNA cleavage (2016)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2016-02-04
    Description: Bacterial adaptive immunity and genome engineering involving the CRISPR (clustered regularly interspaced short palindromic repeats)-associated (Cas) protein Cas9 begin with RNA-guided DNA unwinding to form an RNA-DNA hybrid and a displaced DNA strand inside the protein. The role of this R-loop structure in positioning each DNA strand for cleavage by the two Cas9 nuclease domains is unknown. We determine molecular structures of the catalytically active Streptococcus pyogenes Cas9 R-loop that show the displaced DNA strand located near the RuvC nuclease domain active site. These protein-DNA interactions, in turn, position the HNH nuclease domain adjacent to the target DNA strand cleavage site in a conformation essential for concerted DNA cutting. Cas9 bends the DNA helix by 30 degrees , providing the structural distortion needed for R-loop formation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jiang, Fuguo -- Taylor, David W -- Chen, Janice S -- Kornfeld, Jack E -- Zhou, Kaihong -- Thompson, Aubri J -- Nogales, Eva -- Doudna, Jennifer A -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2016 Feb 19;351(6275):867-71. doi: 10.1126/science.aad8282. Epub 2016 Jan 14.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA. ; Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA. California Institute for Quantitative Biosciences, University of California, Berkeley, CA 94720, USA. ; Howard Hughes Medical Institute, University of California, Berkeley, CA 94720, USA. ; Department of Chemistry, University of California, Berkeley, CA 94720, USA. ; Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA. California Institute for Quantitative Biosciences, University of California, Berkeley, CA 94720, USA. Howard Hughes Medical Institute, University of California, Berkeley, CA 94720, USA. Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA. doudna@berkeley.edu enogales@lbl.gov. ; Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA. California Institute for Quantitative Biosciences, University of California, Berkeley, CA 94720, USA. Howard Hughes Medical Institute, University of California, Berkeley, CA 94720, USA. Department of Chemistry, University of California, Berkeley, CA 94720, USA. Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA. Physical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA. doudna@berkeley.edu enogales@lbl.gov.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26841432" target="_blank"〉PubMed〈/a〉
    Keywords: *CRISPR-Cas Systems ; Catalytic Domain ; *Clustered Regularly Interspaced Short Palindromic Repeats ; Crystallography, X-Ray ; DNA/*chemistry ; *DNA Cleavage ; Endonucleases/*chemistry/ultrastructure ; Genetic Engineering ; Genome ; Nucleic Acid Conformation ; Protein Conformation ; RNA/chemistry ; RNA, Guide ; Streptococcus pyogenes/*enzymology
    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
  • 11
    facet.materialart.
    Unknown
    HIV-1 broadly neutralizing antibody precursor B cells revealed by germline-targeting immunogen (2016)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2016-03-26
    Description: Induction of broadly neutralizing antibodies (bnAbs) is a major HIV vaccine goal. Germline-targeting immunogens aim to initiate bnAb induction by activating bnAb germline precursor B cells. Critical unmet challenges are to determine whether bnAb precursor naive B cells bind germline-targeting immunogens and occur at sufficient frequency in humans for reliable vaccine responses. Using deep mutational scanning and multitarget optimization, we developed a germline-targeting immunogen (eOD-GT8) for diverse VRC01-class bnAbs. We then used the immunogen to isolate VRC01-class precursor naive B cells from HIV-uninfected donors. Frequencies of true VRC01-class precursors, their structures, and their eOD-GT8 affinities support this immunogen as a candidate human vaccine prime. These methods could be applied to germline targeting for other classes of HIV bnAbs and for Abs to other pathogens.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4872700/" 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/PMC4872700/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jardine, Joseph G -- Kulp, Daniel W -- Havenar-Daughton, Colin -- Sarkar, Anita -- Briney, Bryan -- Sok, Devin -- Sesterhenn, Fabian -- Ereno-Orbea, June -- Kalyuzhniy, Oleksandr -- Deresa, Isaiah -- Hu, Xiaozhen -- Spencer, Skye -- Jones, Meaghan -- Georgeson, Erik -- Adachi, Yumiko -- Kubitz, Michael -- deCamp, Allan C -- Julien, Jean-Philippe -- Wilson, Ian A -- Burton, Dennis R -- Crotty, Shane -- Schief, William R -- P01 AI094419/AI/NIAID NIH HHS/ -- P01 AI110657/AI/NIAID NIH HHS/ -- P41GM103393/GM/NIGMS NIH HHS/ -- R01 AI084817/AI/NIAID NIH HHS/ -- UM1 AI100663/AI/NIAID NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2016 Mar 25;351(6280):1458-63. doi: 10.1126/science.aad9195.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA. IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA. Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA. ; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA. Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA. ; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA. Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA. Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA. ; Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA. ; Program in Molecular Structure and Function, Hospital for Sick Children Research Institute, Toronto, Ontario M5G 0A4, Canada. ; Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA. Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA. ; Vaccine and Infectious Disease Division, Statistical Center for HIV/AIDS Research and Prevention (SCHARP), Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA. ; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA. Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA. Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA. Program in Molecular Structure and Function, Hospital for Sick Children Research Institute, Toronto, Ontario M5G 0A4, Canada. Departments of Biochemistry and Immunology, University of Toronto, Toronto, Ontario M5S 1A8, Canada. ; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA. Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA. Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA. Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA. ; Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA. IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA. Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA. Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02129, USA. ; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA. Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA. Division of Infectious Diseases, Department of Medicine, University of California San Diego School of Medicine, La Jolla, CA, USA. schief@scripps.edu shane@lji.org. ; Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA. IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA. Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA. Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02129, USA. schief@scripps.edu shane@lji.org.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27013733" target="_blank"〉PubMed〈/a〉
    Keywords: AIDS Vaccines/*immunology ; Amino Acid Sequence ; Antibodies, Monoclonal/chemistry/*immunology/isolation & purification ; Antibodies, Neutralizing/chemistry/*immunology/isolation & purification ; Antibody Affinity ; B-Lymphocytes/immunology ; Cell Separation ; Combinatorial Chemistry Techniques ; Epitopes, B-Lymphocyte/chemistry/genetics/*immunology ; Germ Cells/*immunology ; HIV Antibodies/chemistry/*immunology/isolation & purification ; HIV-1/*immunology ; Humans ; Molecular Sequence Data ; Mutation ; Peptide Library ; Precursor Cells, B-Lymphoid/*immunology ; 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
  • 12
    facet.materialart.
    Unknown
    beta-Arrestin biosensors reveal a rapid, receptor-dependent activation/deactivation cycle (2016)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2016-03-24
    Description: (beta-)Arrestins are important regulators of G-protein-coupled receptors (GPCRs). They bind to active, phosphorylated GPCRs and thereby shut off 'classical' signalling to G proteins, trigger internalization of GPCRs via interaction with the clathrin machinery and mediate signalling via 'non-classical' pathways. In addition to two visual arrestins that bind to rod and cone photoreceptors (termed arrestin1 and arrestin4), there are only two (non-visual) beta-arrestin proteins (beta-arrestin1 and beta-arrestin2, also termed arrestin2 and arrestin3), which regulate hundreds of different (non-visual) GPCRs. Binding of these proteins to GPCRs usually requires the active form of the receptors plus their phosphorylation by G-protein-coupled receptor kinases (GRKs). The binding of receptors or their carboxy terminus as well as certain truncations induce active conformations of (beta-)arrestins that have recently been solved by X-ray crystallography. Here we investigate both the interaction of beta-arrestin with GPCRs, and the beta-arrestin conformational changes in real time and in living human cells, using a series of fluorescence resonance energy transfer (FRET)-based beta-arrestin2 biosensors. We observe receptor-specific patterns of conformational changes in beta-arrestin2 that occur rapidly after the receptor-beta-arrestin2 interaction. After agonist removal, these changes persist for longer than the direct receptor interaction. Our data indicate a rapid, receptor-type-specific, two-step binding and activation process between GPCRs and beta-arrestins. They further indicate that beta-arrestins remain active after dissociation from receptors, allowing them to remain at the cell surface and presumably signal independently. Thus, GPCRs trigger a rapid, receptor-specific activation/deactivation cycle of beta-arrestins, which permits their active signalling.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nuber, Susanne -- Zabel, Ulrike -- Lorenz, Kristina -- Nuber, Andreas -- Milligan, Graeme -- Tobin, Andrew B -- Lohse, Martin J -- Hoffmann, Carsten -- 1 R01 DA038882/DA/NIDA NIH HHS/ -- BB/K019864/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- England -- Nature. 2016 Mar 31;531(7596):661-4. doi: 10.1038/nature17198. Epub 2016 Mar 23.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Pharmacology and Toxicology, University of Wurzburg, Versbacher Str. 9, 97078 Wurzburg, Germany. ; Rudolf Virchow Center, University of Wurzburg, Versbacher Str. 9, 97078 Wurzburg, Germany. ; Comprehensive Heart Failure Center, University of Wurzburg, Versbacher Str. 9, 97078 Wurzburg, Germany. ; Molecular Pharmacology Group, Institute of Molecular, Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8QQ, UK. ; MRC Toxicology Unit, University of Leicester, Hodgkin Building, Lancaster Road, Leicester LE1 9HN, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27007855" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Arrestins/chemistry/*metabolism ; Biosensing Techniques ; Cattle ; Cell Line ; Cell Membrane/metabolism ; Cell Survival ; Crystallography, X-Ray ; Fluorescence Resonance Energy Transfer ; Humans ; Kinetics ; Models, Molecular ; Protein Binding ; Protein Conformation ; Receptors, G-Protein-Coupled/chemistry/*metabolism ; Signal Transduction ; Substrate Specificity ; 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
  • 13
    facet.materialart.
    Unknown
    The conformational signature of beta-arrestin2 predicts its trafficking and signalling functions (2016)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2016-03-24
    Description: Arrestins are cytosolic proteins that regulate G-protein-coupled receptor (GPCR) desensitization, internalization, trafficking and signalling. Arrestin recruitment uncouples GPCRs from heterotrimeric G proteins, and targets the proteins for internalization via clathrin-coated pits. Arrestins also function as ligand-regulated scaffolds that recruit multiple non-G-protein effectors into GPCR-based 'signalsomes'. Although the dominant function(s) of arrestins vary between receptors, the mechanism whereby different GPCRs specify these divergent functions is unclear. Using a panel of intramolecular fluorescein arsenical hairpin (FlAsH) bioluminescence resonance energy transfer (BRET) reporters to monitor conformational changes in beta-arrestin2, here we show that GPCRs impose distinctive arrestin 'conformational signatures' that reflect the stability of the receptor-arrestin complex and role of beta-arrestin2 in activating or dampening downstream signalling events. The predictive value of these signatures extends to structurally distinct ligands activating the same GPCR, such that the innate properties of the ligand are reflected as changes in beta-arrestin2 conformation. Our findings demonstrate that information about ligand-receptor conformation is encoded within the population average beta-arrestin2 conformation, and provide insight into how different GPCRs can use a common effector for different purposes. This approach may have application in the characterization and development of functionally selective GPCR ligands and in identifying factors that dictate arrestin conformation and function.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lee, Mi-Hye -- Appleton, Kathryn M -- Strungs, Erik G -- Kwon, Joshua Y -- Morinelli, Thomas A -- Peterson, Yuri K -- Laporte, Stephane A -- Luttrell, Louis M -- DK055524/DK/NIDDK NIH HHS/ -- GM095497/GM/NIGMS NIH HHS/ -- MOP-74603/Canadian Institutes of Health Research/Canada -- R01 DK055524/DK/NIDDK NIH HHS/ -- R01 GM095497/GM/NIGMS NIH HHS/ -- RR027777/RR/NCRR NIH HHS/ -- S10 RR027777/RR/NCRR NIH HHS/ -- England -- Nature. 2016 Mar 31;531(7596):665-8. doi: 10.1038/nature17154. Epub 2016 Mar 23.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine, Medical University of South Carolina, Charleston, South Carolina 29425, USA. ; Department of Pharmaceutical &Biomedical Sciences, College of Pharmacy, Medical University of South Carolina, Charleston, South Carolina 29425, USA. ; Department of Medicine, McGill University Health Center Research Institute, McGill University, Quebec H4A 3J1, Canada. ; Pharmacology and Therapeutics, McGill University, Quebec H3G 1Y6, Canada. ; Anatomy and Cell Biology, McGill University, Quebec H3A 0C7, Canada. ; Research Service of the Ralph H. Johnson Veterans Affairs Medical Center, Charleston, South Carolina 29401, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27007854" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Arrestins/*chemistry/*metabolism ; Enzyme Activation ; HEK293 Cells ; Humans ; Ligands ; Mitogen-Activated Protein Kinase 1/metabolism ; Mitogen-Activated Protein Kinase 3/metabolism ; Protein Conformation ; Protein Transport ; Rats ; Receptors, G-Protein-Coupled/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
  • 14
    facet.materialart.
    Unknown
    A mechanism of viral immune evasion revealed by cryo-EM analysis of the TAP transporter (2016)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2016-01-21
    Description: Cellular immunity against viral infection and tumour cells depends on antigen presentation by major histocompatibility complex class I (MHC I) molecules. Intracellular antigenic peptides are transported into the endoplasmic reticulum by the transporter associated with antigen processing (TAP) and then loaded onto the nascent MHC I molecules, which are exported to the cell surface and present peptides to the immune system. Cytotoxic T lymphocytes recognize non-self peptides and program the infected or malignant cells for apoptosis. Defects in TAP account for immunodeficiency and tumour development. To escape immune surveillance, some viruses have evolved strategies either to downregulate TAP expression or directly inhibit TAP activity. So far, neither the architecture of TAP nor the mechanism of viral inhibition has been elucidated at the structural level. Here we describe the cryo-electron microscopy structure of human TAP in complex with its inhibitor ICP47, a small protein produced by the herpes simplex virus I. Here we show that the 12 transmembrane helices and 2 cytosolic nucleotide-binding domains of the transporter adopt an inward-facing conformation with the two nucleotide-binding domains separated. The viral inhibitor ICP47 forms a long helical hairpin, which plugs the translocation pathway of TAP from the cytoplasmic side. Association of ICP47 precludes substrate binding and prevents nucleotide-binding domain closure necessary for ATP hydrolysis. This work illustrates a striking example of immune evasion by persistent viruses. By blocking viral antigens from entering the endoplasmic reticulum, herpes simplex virus is hidden from cytotoxic T lymphocytes, which may contribute to establishing a lifelong infection in the host.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Oldham, Michael L -- Hite, Richard K -- Steffen, Alanna M -- Damko, Ermelinda -- Li, Zongli -- Walz, Thomas -- Chen, Jue -- Howard Hughes Medical Institute/ -- England -- Nature. 2016 Jan 28;529(7587):537-40. doi: 10.1038/nature16506. Epub 2016 Jan 20.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Rockefeller University, 1230 York Avenue, New York, New York 10065, USA. ; Howard Hughes Medical Institute, 4000 Jones Bridge Road, Chevy Chase, Maryland 20815, USA. ; Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, Massachusetts 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26789246" target="_blank"〉PubMed〈/a〉
    Keywords: ATP-Binding Cassette Transporters/antagonists & ; inhibitors/chemistry/*metabolism/*ultrastructure ; Amino Acid Sequence ; Antigens, Viral/immunology/metabolism ; *Cryoelectron Microscopy ; Endoplasmic Reticulum/metabolism ; Herpesvirus 1, Human/chemistry/*immunology/metabolism/ultrastructure ; Immediate-Early Proteins/chemistry/*metabolism/*ultrastructure ; *Immune Evasion ; Models, Molecular ; Molecular Sequence Data ; Protein Binding ; 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
  • 15
    facet.materialart.
    Unknown
    Structural disorder of monomeric alpha-synuclein persists in mammalian cells (2016)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2016-01-26
    Description: Intracellular aggregation of the human amyloid protein alpha-synuclein is causally linked to Parkinson's disease. While the isolated protein is intrinsically disordered, its native structure in mammalian cells is not known. Here we use nuclear magnetic resonance (NMR) and electron paramagnetic resonance (EPR) spectroscopy to derive atomic-resolution insights into the structure and dynamics of alpha-synuclein in different mammalian cell types. We show that the disordered nature of monomeric alpha-synuclein is stably preserved in non-neuronal and neuronal cells. Under physiological cell conditions, alpha-synuclein is amino-terminally acetylated and adopts conformations that are more compact than when in buffer, with residues of the aggregation-prone non-amyloid-beta component (NAC) region shielded from exposure to the cytoplasm, which presumably counteracts spontaneous aggregation. These results establish that different types of crowded intracellular environments do not inherently promote alpha-synuclein oligomerization and, more generally, that intrinsic structural disorder is sustainable in mammalian cells.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Theillet, Francois-Xavier -- Binolfi, Andres -- Bekei, Beata -- Martorana, Andrea -- Rose, Honor May -- Stuiver, Marchel -- Verzini, Silvia -- Lorenz, Dorothea -- van Rossum, Marleen -- Goldfarb, Daniella -- Selenko, Philipp -- England -- Nature. 2016 Feb 4;530(7588):45-50. doi: 10.1038/nature16531. Epub 2016 Jan 25.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉In-Cell NMR Laboratory, Department of NMR-supported Structural Biology, Leibniz Institute of Molecular Pharmacology (FMP Berlin), Robert-Rossle Strasse 10, 13125 Berlin, Germany. ; Department of Chemical Physics, Weizmann Institute of Science, Rehovot 76100, Israel. ; Department of Molecular Physiology and Cell Biology, Leibniz Institute of Molecular Pharmacology (FMP Berlin), Robert-Rossle Strasse 10, 13125 Berlin, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26808899" target="_blank"〉PubMed〈/a〉
    Keywords: Acetylation ; Cell Line ; Cytoplasm/chemistry/metabolism ; Electron Spin Resonance Spectroscopy ; HeLa Cells ; Humans ; Intracellular Space/*chemistry/*metabolism ; Neurons/cytology/metabolism ; Nuclear Magnetic Resonance, Biomolecular ; Protein Conformation ; alpha-Synuclein/*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
  • 16
    facet.materialart.
    Unknown
    Long-sought biological compass discovered (2015)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2015-11-20
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cyranoski, David -- England -- Nature. 2015 Nov 19;527(7578):283-4. doi: 10.1038/527283a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26581268" target="_blank"〉PubMed〈/a〉
    Keywords: Animal Migration/physiology ; Animals ; Circadian Rhythm/physiology ; Cryptochromes/metabolism ; Drosophila Proteins/chemistry/*metabolism ; Drosophila melanogaster/*physiology ; *Earth (Planet) ; Humans ; Iron/metabolism ; Iron-Sulfur Proteins/chemistry/*metabolism ; *Magnetic Fields ; Models, Molecular ; Protein Conformation ; Spatial Navigation/*physiology ; Whales/physiology
    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
    Conformational dynamics of a class C G-protein-coupled receptor (2015)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2015-08-11
    Description: G-protein-coupled receptors (GPCRs) constitute the largest family of membrane receptors in eukaryotes. Crystal structures have provided insight into GPCR interactions with ligands and G proteins, but our understanding of the conformational dynamics of activation is incomplete. Metabotropic glutamate receptors (mGluRs) are dimeric class C GPCRs that modulate neuronal excitability, synaptic plasticity, and serve as drug targets for neurological disorders. A 'clamshell' ligand-binding domain (LBD), which contains the ligand-binding site, is coupled to the transmembrane domain via a cysteine-rich domain, and LBD closure seems to be the first step in activation. Crystal structures of isolated mGluR LBD dimers led to the suggestion that activation also involves a reorientation of the dimer interface from a 'relaxed' to an 'active' state, but the relationship between ligand binding, LBD closure and dimer interface rearrangement in activation remains unclear. Here we use single-molecule fluorescence resonance energy transfer to probe the activation mechanism of full-length mammalian group II mGluRs. We show that the LBDs interconvert between three conformations: resting, activated and a short-lived intermediate state. Orthosteric agonists induce transitions between these conformational states, with efficacy determined by occupancy of the active conformation. Unlike mGluR2, mGluR3 displays basal dynamics, which are Ca(2+)-dependent and lead to basal protein activation. Our results support a general mechanism for the activation of mGluRs in which agonist binding induces closure of the LBDs, followed by dimer interface reorientation. Our experimental strategy should be widely applicable to study conformational dynamics in GPCRs and other membrane proteins.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4597782/" 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/PMC4597782/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Vafabakhsh, Reza -- Levitz, Joshua -- Isacoff, Ehud Y -- 2PN2EY018241/EY/NEI NIH HHS/ -- PN2 EY018241/EY/NEI NIH HHS/ -- England -- Nature. 2015 Aug 27;524(7566):497-501. doi: 10.1038/nature14679. Epub 2015 Aug 10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Cell Biology, University of California, Berkeley, California 94720, USA. ; Helen Wills Neuroscience Institute, University of California, Berkeley, California 94720, USA. ; Physical Bioscience Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26258295" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Binding Sites ; Drug Partial Agonism ; *Fluorescence Resonance Energy Transfer ; Humans ; Ligands ; Models, Biological ; Models, Molecular ; Protein Binding ; Protein Conformation ; Rats ; Receptors, Metabotropic Glutamate/*chemistry/*classification/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
  • 18
    facet.materialart.
    Unknown
    Structural basis of JAZ repression of MYC transcription factors in jasmonate signalling (2015)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2015-08-11
    Description: The plant hormone jasmonate plays crucial roles in regulating plant responses to herbivorous insects and microbial pathogens and is an important regulator of plant growth and development. Key mediators of jasmonate signalling include MYC transcription factors, which are repressed by jasmonate ZIM-domain (JAZ) transcriptional repressors in the resting state. In the presence of active jasmonate, JAZ proteins function as jasmonate co-receptors by forming a hormone-dependent complex with COI1, the F-box subunit of an SCF-type ubiquitin E3 ligase. The hormone-dependent formation of the COI1-JAZ co-receptor complex leads to ubiquitination and proteasome-dependent degradation of JAZ repressors and release of MYC proteins from transcriptional repression. The mechanism by which JAZ proteins repress MYC transcription factors and how JAZ proteins switch between the repressor function in the absence of hormone and the co-receptor function in the presence of hormone remain enigmatic. Here we show that Arabidopsis MYC3 undergoes pronounced conformational changes when bound to the conserved Jas motif of the JAZ9 repressor. The Jas motif, previously shown to bind to hormone as a partly unwound helix, forms a complete alpha-helix that displaces the amino (N)-terminal helix of MYC3 and becomes an integral part of the MYC N-terminal fold. In this position, the Jas helix competitively inhibits MYC3 interaction with the MED25 subunit of the transcriptional Mediator complex. Our structural and functional studies elucidate a dynamic molecular switch mechanism that governs the repression and activation of a major plant hormone pathway.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4567411/" 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/PMC4567411/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhang, Feng -- Yao, Jian -- Ke, Jiyuan -- Zhang, Li -- Lam, Vinh Q -- Xin, Xiu-Fang -- Zhou, X Edward -- Chen, Jian -- Brunzelle, Joseph -- Griffin, Patrick R -- Zhou, Mingguo -- Xu, H Eric -- Melcher, Karsten -- He, Sheng Yang -- R01 AI068718/AI/NIAID NIH HHS/ -- R01 GM102545/GM/NIGMS NIH HHS/ -- R01AI060761/AI/NIAID NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2015 Sep 10;525(7568):269-73. doi: 10.1038/nature14661. Epub 2015 Aug 10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Structural Sciences and Laboratory of Structural Biology and Biochemistry, Van Andel Research Institute, Grand Rapids, Michigan 49503, USA. ; DOE Plant Research Laboratory, Michigan State University, East Lansing, Michigan 48824, USA. ; College of Plant Protection, Nanjing Agricultural University, No. 1 Weigang, 210095, Nanjing, Jiangsu Province, China. ; Department of Biological Sciences, Western Michigan University, Kalamazoo, Michigan 49008, USA. ; Department of Plant Biology, Michigan State University, East Lansing, Michigan 48824, USA. ; Department of Molecular Therapeutics, Translational Research Institute, The Scripps Research Institute, Scripps Florida, Jupiter, Florida 33458, USA. ; College of Life Sciences, Zhejiang Sci-Tech University, Hangzhou 310018, Zhejiang, China. ; Department of Molecular Pharmacology and Biological Chemistry, Life Sciences Collaborative Access Team, Synchrotron Research Center, Northwestern University, Argonne, Illinois 60439, USA. ; Key Laboratory of Receptor Research, VARI-SIMM Center, Center for Structure and Function of Drug Targets, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China. ; Howard Hughes Medical Institute, Michigan State University, East Lansing, Michigan 48824, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26258305" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Motifs ; Apoproteins/chemistry/metabolism ; *Arabidopsis/chemistry/metabolism ; Arabidopsis Proteins/*antagonists & inhibitors/*chemistry/genetics/*metabolism ; Binding, Competitive/genetics ; Crystallography, X-Ray ; Cyclopentanes/*metabolism ; Models, Molecular ; Nuclear Proteins/metabolism ; Oxylipins/*metabolism ; Plant Growth Regulators/*metabolism ; Proteasome Endopeptidase Complex/metabolism ; Protein Binding/genetics ; Protein Conformation ; Repressor Proteins/*chemistry/genetics/*metabolism ; *Signal Transduction ; Trans-Activators/*antagonists & inhibitors/*chemistry/genetics/metabolism ; Ubiquitination
    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
    Electron cryomicroscopy observation of rotational states in a eukaryotic V-ATPase (2015)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2015-05-15
    Description: Eukaryotic vacuolar H(+)-ATPases (V-ATPases) are rotary enzymes that use energy from hydrolysis of ATP to ADP to pump protons across membranes and control the pH of many intracellular compartments. ATP hydrolysis in the soluble catalytic region of the enzyme is coupled to proton translocation through the membrane-bound region by rotation of a central rotor subcomplex, with peripheral stalks preventing the entire membrane-bound region from turning with the rotor. The eukaryotic V-ATPase is the most complex rotary ATPase: it has three peripheral stalks, a hetero-oligomeric proton-conducting proteolipid ring, several subunits not found in other rotary ATPases, and is regulated by reversible dissociation of its catalytic and proton-conducting regions. Studies of ATP synthases, V-ATPases, and bacterial/archaeal V/A-ATPases have suggested that flexibility is necessary for the catalytic mechanism of rotary ATPases, but the structures of different rotational states have never been observed experimentally. Here we use electron cryomicroscopy to obtain structures for three rotational states of the V-ATPase from the yeast Saccharomyces cerevisiae. The resulting series of structures shows ten proteolipid subunits in the c-ring, setting the ATP:H(+) ratio for proton pumping by the V-ATPase at 3:10, and reveals long and highly tilted transmembrane alpha-helices in the a-subunit that interact with the c-ring. The three different maps reveal the conformational changes that occur to couple rotation in the symmetry-mismatched soluble catalytic region to the membrane-bound proton-translocating region. Almost all of the subunits of the enzyme undergo conformational changes during the transitions between these three rotational states. The structures of these states provide direct evidence that deformation during rotation enables the smooth transmission of power through rotary ATPases.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhao, Jianhua -- Benlekbir, Samir -- Rubinstein, John L -- MOP 81294/Canadian Institutes of Health Research/Canada -- England -- Nature. 2015 May 14;521(7551):241-5. doi: 10.1038/nature14365.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Molecular Structure and Function Program, The Hospital for Sick Children Research Institute, 686 Bay Street, Toronto, Ontario M5G 0A4, Canada [2] Department of Medical Biophysics, The University of Toronto, Toronto Medical Discovery Tower, MaRS Centre, 101 College Street, Toronto, Ontario M5G 1L7, Canada. ; Molecular Structure and Function Program, The Hospital for Sick Children Research Institute, 686 Bay Street, Toronto, Ontario M5G 0A4, Canada. ; 1] Molecular Structure and Function Program, The Hospital for Sick Children Research Institute, 686 Bay Street, Toronto, Ontario M5G 0A4, Canada [2] Department of Medical Biophysics, The University of Toronto, Toronto Medical Discovery Tower, MaRS Centre, 101 College Street, Toronto, Ontario M5G 1L7, Canada [3] Department of Biochemistry, The University of Toronto, 1 King's College Circle, Medical Sciences Building, Toronto, Ontario M5S 1A8, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25971514" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphate/metabolism ; Biocatalysis ; Cell Membrane/chemistry/enzymology/metabolism ; *Cryoelectron Microscopy ; Lipid Bilayers/metabolism ; Models, Molecular ; Pliability ; Protein Conformation ; Protein Subunits/chemistry/metabolism ; Protons ; *Rotation ; Saccharomyces cerevisiae/*enzymology ; Solubility ; Vacuolar Proton-Translocating ATPases/*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
  • 20
    facet.materialart.
    Unknown
    Structure and mechanism of an active lipid-linked oligosaccharide flippase (2015)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2015-08-13
    Description: The flipping of membrane-embedded lipids containing large, polar head groups is slow and energetically unfavourable, and is therefore catalysed by flippases, the mechanisms of which are unknown. A prominent example of a flipping reaction is the translocation of lipid-linked oligosaccharides that serve as donors in N-linked protein glycosylation. In Campylobacter jejuni, this process is catalysed by the ABC transporter PglK. Here we present a mechanism of PglK-catalysed lipid-linked oligosaccharide flipping based on crystal structures in distinct states, a newly devised in vitro flipping assay, and in vivo studies. PglK can adopt inward- and outward-facing conformations in vitro, but only outward-facing states are required for flipping. While the pyrophosphate-oligosaccharide head group of lipid-linked oligosaccharides enters the translocation cavity and interacts with positively charged side chains, the lipidic polyprenyl tail binds and activates the transporter but remains exposed to the lipid bilayer during the reaction. The proposed mechanism is distinct from the classical alternating-access model applied to other transporters.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Perez, Camilo -- Gerber, Sabina -- Boilevin, Jeremy -- Bucher, Monika -- Darbre, Tamis -- Aebi, Markus -- Reymond, Jean-Louis -- Locher, Kaspar P -- England -- Nature. 2015 Aug 27;524(7566):433-8. doi: 10.1038/nature14953. Epub 2015 Aug 12.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Molecular Biology and Biophysics, ETH Zurich, CH-8093 Zurich, Switzerland. ; Department of Chemistry and Biochemistry, University of Berne, CH-3012 Berne, Switzerland. ; Institute of Microbiology, ETH Zurich, CH-8093 Zurich, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26266984" target="_blank"〉PubMed〈/a〉
    Keywords: ATP-Binding Cassette Transporters/*chemistry/*metabolism ; Adenosine Triphosphatases/chemistry/metabolism ; Adenosine Triphosphate/metabolism ; *Biocatalysis ; Campylobacter jejuni/cytology/*enzymology/metabolism ; Crystallography, X-Ray ; Hydrolysis ; Lipid Bilayers/metabolism ; Lipopolysaccharides/*metabolism ; Models, Molecular ; Protein Conformation ; 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
  • 21
    facet.materialart.
    Unknown
    In situ structural analysis of the human nuclear pore complex (2015)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2015-09-30
    Description: Nuclear pore complexes are fundamental components of all eukaryotic cells that mediate nucleocytoplasmic exchange. Determining their 110-megadalton structure imposes a formidable challenge and requires in situ structural biology approaches. Of approximately 30 nucleoporins (Nups), 15 are structured and form the Y and inner-ring complexes. These two major scaffolding modules assemble in multiple copies into an eight-fold rotationally symmetric structure that fuses the inner and outer nuclear membranes to form a central channel of ~60 nm in diameter. The scaffold is decorated with transport-channel Nups that often contain phenylalanine-repeat sequences and mediate the interaction with cargo complexes. Although the architectural arrangement of parts of the Y complex has been elucidated, it is unclear how exactly it oligomerizes in situ. Here we combine cryo-electron tomography with mass spectrometry, biochemical analysis, perturbation experiments and structural modelling to generate, to our knowledge, the most comprehensive architectural model of the human nuclear pore complex to date. Our data suggest previously unknown protein interfaces across Y complexes and to inner-ring complex members. We show that the transport-channel Nup358 (also known as Ranbp2) has a previously unanticipated role in Y-complex oligomerization. Our findings blur the established boundaries between scaffold and transport-channel Nups. We conclude that, similar to coated vesicles, several copies of the same structural building block--although compositionally identical--engage in different local sets of interactions and conformations.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉von Appen, Alexander -- Kosinski, Jan -- Sparks, Lenore -- Ori, Alessandro -- DiGuilio, Amanda L -- Vollmer, Benjamin -- Mackmull, Marie-Therese -- Banterle, Niccolo -- Parca, Luca -- Kastritis, Panagiotis -- Buczak, Katarzyna -- Mosalaganti, Shyamal -- Hagen, Wim -- Andres-Pons, Amparo -- Lemke, Edward A -- Bork, Peer -- Antonin, Wolfram -- Glavy, Joseph S -- Bui, Khanh Huy -- Beck, Martin -- 1R21AG047433-01/AG/NIA NIH HHS/ -- England -- Nature. 2015 Oct 1;526(7571):140-3. doi: 10.1038/nature15381. Epub 2015 Sep 23.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉European Molecular Biology Laboratory, Structural and Computational Biology Unit, 69117 Heidelberg, Germany. ; Department of Chemistry, Chemical Biology and Biomedical Engineering, Stevens Institute of Technology, 507 River St., Hoboken, New Jersey 07030, USA. ; Friedrich Miescher Laboratory of the Max Planck Society, Spemannstrasse 39, 72076 Tubingen, Germany. ; Department of Anatomy and Cell Biology, McGill University, Montreal, Quebec H3A 0C7, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26416747" target="_blank"〉PubMed〈/a〉
    Keywords: Binding Sites ; *Cryoelectron Microscopy ; HeLa Cells ; Humans ; Mass Spectrometry ; Models, Molecular ; Molecular Chaperones/chemistry/metabolism/ultrastructure ; Nuclear Envelope/metabolism ; Nuclear Pore/*chemistry/metabolism/*ultrastructure ; Nuclear Pore Complex Proteins/*chemistry/metabolism/*ultrastructure ; Protein Conformation ; Protein Multimerization ; Protein Stability
    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
    Crystal structures of a double-barrelled fluoride ion channel (2015)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2015-09-08
    Description: To contend with hazards posed by environmental fluoride, microorganisms export this anion through F(-)-specific ion channels of the Fluc family. Since the recent discovery of Fluc channels, numerous idiosyncratic features of these proteins have been unearthed, including strong selectivity for F(-) over Cl(-) and dual-topology dimeric assembly. To understand the chemical basis for F(-) permeation and how the antiparallel subunits convene to form a F(-)-selective pore, here we solve the crystal structures of two bacterial Fluc homologues in complex with three different monobody inhibitors, with and without F(-) present, to a maximum resolution of 2.1 A. The structures reveal a surprising 'double-barrelled' channel architecture in which two F(-) ion pathways span the membrane, and the dual-topology arrangement includes a centrally coordinated cation, most likely Na(+). F(-) selectivity is proposed to arise from the very narrow pores and an unusual anion coordination that exploits the quadrupolar edges of conserved phenylalanine rings.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Stockbridge, Randy B -- Kolmakova-Partensky, Ludmila -- Shane, Tania -- Koide, Akiko -- Koide, Shohei -- Miller, Christopher -- Newstead, Simon -- 102890/Z/13/Z/Wellcome Trust/United Kingdom -- K99 GM111767/GM/NIGMS NIH HHS/ -- K99-GM-111767/GM/NIGMS NIH HHS/ -- R01 GM107023/GM/NIGMS NIH HHS/ -- R01-GM107023/GM/NIGMS NIH HHS/ -- U54 GM087519/GM/NIGMS NIH HHS/ -- U54-GM087519/GM/NIGMS NIH HHS/ -- England -- Nature. 2015 Sep 24;525(7570):548-51. doi: 10.1038/nature14981. Epub 2015 Sep 7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, Howard Hughes Medical Institute, Brandeis University, Waltham, Massachusetts 02454, USA. ; Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, Illinois 60637, USA. ; Department of Physiology, Anatomy, and Genetics, University of Oxford, Oxford OX1 3QU, UK. ; Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26344196" target="_blank"〉PubMed〈/a〉
    Keywords: Anions/chemistry/metabolism/pharmacology ; Bacterial Proteins/*chemistry/*metabolism ; Cell Membrane/metabolism ; Crystallography, X-Ray ; Fluorides/chemistry/*metabolism/*pharmacology ; Ion Channels/*chemistry/*metabolism ; Models, Biological ; Models, Molecular ; Phenylalanine/metabolism ; 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
    Crystal structures of the human adiponectin receptors (2015)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2015-04-10
    Description: Adiponectin stimulation of its receptors, AdipoR1 and AdipoR2, increases the activities of 5' AMP-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor (PPAR), respectively, thereby contributing to healthy longevity as key anti-diabetic molecules. AdipoR1 and AdipoR2 were predicted to contain seven transmembrane helices with the opposite topology to G-protein-coupled receptors. Here we report the crystal structures of human AdipoR1 and AdipoR2 at 2.9 and 2.4 A resolution, respectively, which represent a novel class of receptor structure. The seven-transmembrane helices, conformationally distinct from those of G-protein-coupled receptors, enclose a large cavity where three conserved histidine residues coordinate a zinc ion. The zinc-binding structure may have a role in the adiponectin-stimulated AMPK phosphorylation and UCP2 upregulation. Adiponectin may broadly interact with the extracellular face, rather than the carboxy-terminal tail, of the receptors. The present information will facilitate the understanding of novel structure-function relationships and the development and optimization of AdipoR agonists for the treatment of obesity-related diseases, such as type 2 diabetes.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4477036/" 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/PMC4477036/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tanabe, Hiroaki -- Fujii, Yoshifumi -- Okada-Iwabu, Miki -- Iwabu, Masato -- Nakamura, Yoshihiro -- Hosaka, Toshiaki -- Motoyama, Kanna -- Ikeda, Mariko -- Wakiyama, Motoaki -- Terada, Takaho -- Ohsawa, Noboru -- Hato, Masakatsu -- Ogasawara, Satoshi -- Hino, Tomoya -- Murata, Takeshi -- Iwata, So -- Hirata, Kunio -- Kawano, Yoshiaki -- Yamamoto, Masaki -- Kimura-Someya, Tomomi -- Shirouzu, Mikako -- Yamauchi, Toshimasa -- Kadowaki, Takashi -- Yokoyama, Shigeyuki -- 062164/Z/00/Z/Wellcome Trust/United Kingdom -- 089809/Wellcome Trust/United Kingdom -- BB/G02325/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- BB/G023425/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- England -- Nature. 2015 Apr 16;520(7547):312-6. doi: 10.1038/nature14301. Epub 2015 Apr 8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] RIKEN Systems and Structural Biology Center, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama 230-0045, Japan [2] Department of Biophysics and Biochemistry and Laboratory of Structural Biology, Graduate School of Science, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan [3] Division of Structural and Synthetic Biology, RIKEN Center for Life Science Technologies, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama 230-0045, Japan [4] RIKEN Structural Biology Laboratory, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama 230-0045, Japan. ; 1] RIKEN Systems and Structural Biology Center, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama 230-0045, Japan [2] RIKEN Structural Biology Laboratory, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama 230-0045, Japan. ; 1] Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan [2] Department of Integrated Molecular Science on Metabolic Diseases, 22nd Century Medical and Research Center, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan. ; 1] Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan [2] Department of Integrated Molecular Science on Metabolic Diseases, 22nd Century Medical and Research Center, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan [3] PRESTO, Japan Science and Technology Agency, Kawaguchi, Saitama 332-0012, Japan. ; 1] RIKEN Systems and Structural Biology Center, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama 230-0045, Japan [2] Division of Structural and Synthetic Biology, RIKEN Center for Life Science Technologies, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama 230-0045, Japan [3] RIKEN Structural Biology Laboratory, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama 230-0045, Japan. ; 1] RIKEN Systems and Structural Biology Center, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama 230-0045, Japan [2] Division of Structural and Synthetic Biology, RIKEN Center for Life Science Technologies, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama 230-0045, Japan. ; RIKEN Systems and Structural Biology Center, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama 230-0045, Japan. ; Department of Cell Biology, Graduate School of Medicine, Kyoto University, Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan. ; 1] Department of Cell Biology, Graduate School of Medicine, Kyoto University, Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan [2] JST, Research Acceleration Program, Membrane Protein Crystallography Project, Yoshida-Konoe-cho, Sakyo-ku, Kyoto, 606-8501, Japan. ; 1] RIKEN Systems and Structural Biology Center, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama 230-0045, Japan [2] Department of Cell Biology, Graduate School of Medicine, Kyoto University, Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan [3] JST, Research Acceleration Program, Membrane Protein Crystallography Project, Yoshida-Konoe-cho, Sakyo-ku, Kyoto, 606-8501, Japan [4] Department of Chemistry, Graduate School of Science, Chiba University, Yayoi-cho, Inage, Chiba 263-8522, Japan. ; 1] RIKEN Systems and Structural Biology Center, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama 230-0045, Japan [2] Department of Cell Biology, Graduate School of Medicine, Kyoto University, Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan [3] JST, Research Acceleration Program, Membrane Protein Crystallography Project, Yoshida-Konoe-cho, Sakyo-ku, Kyoto, 606-8501, Japan [4] Division of Molecular Biosciences, Membrane Protein Crystallography Group, Imperial College, London SW7 2AZ, UK [5] Diamond Light Source, Harwell Science and Innovation Campus, Chilton, Didcot, Oxfordshire OX11 0DE, UK [6] RIKEN SPring-8 Center, Harima Institute, Kouto, Sayo, Hyogo 679-5148, Japan. ; RIKEN SPring-8 Center, Harima Institute, Kouto, Sayo, Hyogo 679-5148, Japan. ; 1] Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan [2] Department of Integrated Molecular Science on Metabolic Diseases, 22nd Century Medical and Research Center, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan [3] CREST, Japan Science and Technology Agency, Kawaguchi, Saitama 332-0012, Japan. ; 1] RIKEN Systems and Structural Biology Center, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama 230-0045, Japan [2] Department of Biophysics and Biochemistry and Laboratory of Structural Biology, Graduate School of Science, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan [3] RIKEN Structural Biology Laboratory, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama 230-0045, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25855295" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Binding Sites ; Crystallography, X-Ray ; Histidine/chemistry/metabolism ; Humans ; Models, Molecular ; Molecular Sequence Data ; Protein Conformation ; Receptors, Adiponectin/*chemistry/metabolism ; Structure-Activity Relationship ; Zinc/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
  • 24
    facet.materialart.
    Unknown
    Biology, wet and dry (2015)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2015-08-08
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Teichmann, Sarah -- Pain, Elisabeth -- New York, N.Y. -- Science. 2015 Aug 7;349(6248):662. doi: 10.1126/science.349.6248.662.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Elisabeth Pain is Science Careers contributing editor for Europe. Send your story to SciCareerEditor@aaas.org.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26250686" target="_blank"〉PubMed〈/a〉
    Keywords: *Career Choice ; *Computational Biology ; Molecular Biology ; 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
  • 25
    facet.materialart.
    Unknown
    Structural basis of pre-mRNA splicing (2015)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2015-08-22
    Description: Splicing of precursor messenger RNA is performed by the spliceosome. In the cryogenic electron microscopy structure of the yeast spliceosome, U5 small nuclear ribonucleoprotein acts as a central scaffold onto which U6 and U2 small nuclear RNAs (snRNAs) are intertwined to form a catalytic center next to Loop I of U5 snRNA. Magnesium ions are coordinated by conserved nucleotides in U6 snRNA. The intron lariat is held in place through base-pairing interactions with both U2 and U6 snRNAs, leaving the variable-length middle portion on the solvent-accessible surface of the catalytic center. The protein components of the spliceosome anchor both 5' and 3' ends of the U2 and U6 snRNAs away from the active site, direct the RNA sequences, and allow sufficient flexibility between the ends and the catalytic center. Thus, the spliceosome is in essence a protein-directed ribozyme, with the protein components essential for the delivery of critical RNA molecules into close proximity of one another at the right time for the splicing reaction.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hang, Jing -- Wan, Ruixue -- Yan, Chuangye -- Shi, Yigong -- New York, N.Y. -- Science. 2015 Sep 11;349(6253):1191-8. doi: 10.1126/science.aac8159. Epub 2015 Aug 20.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Ministry of Education Key Laboratory of Protein Science, Tsinghua-Peking Joint Center for Life Sciences, Center for Structural Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China. ; Ministry of Education Key Laboratory of Protein Science, Tsinghua-Peking Joint Center for Life Sciences, Center for Structural Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China. shi-lab@tsinghua.edu.cn.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26292705" target="_blank"〉PubMed〈/a〉
    Keywords: Catalytic Domain ; Exons ; Introns ; Nucleic Acid Conformation ; Protein Conformation ; RNA Precursors/*genetics ; *RNA Splicing ; RNA, Messenger/*biosynthesis/genetics ; RNA, Small Nuclear/chemistry ; Ribonucleoprotein, U5 Small Nuclear/chemistry ; Spliceosomes/*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
  • 26
    facet.materialart.
    Unknown
    K2P channel gating mechanisms revealed by structures of TREK-2 and a complex with Prozac (2015)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2015-03-15
    Description: TREK-2 (KCNK10/K2P10), a two-pore domain potassium (K2P) channel, is gated by multiple stimuli such as stretch, fatty acids, and pH and by several drugs. However, the mechanisms that control channel gating are unclear. Here we present crystal structures of the human TREK-2 channel (up to 3.4 angstrom resolution) in two conformations and in complex with norfluoxetine, the active metabolite of fluoxetine (Prozac) and a state-dependent blocker of TREK channels. Norfluoxetine binds within intramembrane fenestrations found in only one of these two conformations. Channel activation by arachidonic acid and mechanical stretch involves conversion between these states through movement of the pore-lining helices. These results provide an explanation for TREK channel mechanosensitivity, regulation by diverse stimuli, and possible off-target effects of the serotonin reuptake inhibitor Prozac.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dong, Yin Yao -- Pike, Ashley C W -- Mackenzie, Alexandra -- McClenaghan, Conor -- Aryal, Prafulla -- Dong, Liang -- Quigley, Andrew -- Grieben, Mariana -- Goubin, Solenne -- Mukhopadhyay, Shubhashish -- Ruda, Gian Filippo -- Clausen, Michael V -- Cao, Lishuang -- Brennan, Paul E -- Burgess-Brown, Nicola A -- Sansom, Mark S P -- Tucker, Stephen J -- Carpenter, Elisabeth P -- 084655/Wellcome Trust/United Kingdom -- 092809/Z/10/Z/Wellcome Trust/United Kingdom -- Biotechnology and Biological Sciences Research Council/United Kingdom -- New York, N.Y. -- Science. 2015 Mar 13;347(6227):1256-9. doi: 10.1126/science.1261512.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Structural Genomics Consortium, University of Oxford, Oxford OX3 7DQ, UK. ; Structural Genomics Consortium, University of Oxford, Oxford OX3 7DQ, UK. Clarendon Laboratory, Department of Physics, University of Oxford, Oxford OX1 3PU, UK. ; Clarendon Laboratory, Department of Physics, University of Oxford, Oxford OX1 3PU, UK. OXION Initiative in Ion Channels and Disease, University of Oxford, Oxford OX1 3PN, UK. ; Clarendon Laboratory, Department of Physics, University of Oxford, Oxford OX1 3PU, UK. OXION Initiative in Ion Channels and Disease, University of Oxford, Oxford OX1 3PN, UK. Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UK. ; Structural Genomics Consortium, University of Oxford, Oxford OX3 7DQ, UK. Target Discovery Institute, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7FZ, UK. ; Clarendon Laboratory, Department of Physics, University of Oxford, Oxford OX1 3PU, UK. ; Pfizer Neusentis, Granta Park, Cambridge CB21 6GS, UK. ; OXION Initiative in Ion Channels and Disease, University of Oxford, Oxford OX1 3PN, UK. Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UK. ; Clarendon Laboratory, Department of Physics, University of Oxford, Oxford OX1 3PU, UK. OXION Initiative in Ion Channels and Disease, University of Oxford, Oxford OX1 3PN, UK. liz.carpenter@sgc.ox.ac.uk stephen.tucker@physics.ox.ac.uk. ; Structural Genomics Consortium, University of Oxford, Oxford OX3 7DQ, UK. OXION Initiative in Ion Channels and Disease, University of Oxford, Oxford OX1 3PN, UK. liz.carpenter@sgc.ox.ac.uk stephen.tucker@physics.ox.ac.uk.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25766236" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Arachidonic Acid/pharmacology ; Binding Sites ; Crystallography, X-Ray ; Fluoxetine/analogs & derivatives/chemistry/metabolism/pharmacology ; Humans ; *Ion Channel Gating ; Models, Molecular ; Molecular Dynamics Simulation ; Molecular Sequence Data ; Potassium/metabolism ; Potassium Channels, Tandem Pore Domain/antagonists & ; inhibitors/*chemistry/metabolism ; Protein Conformation ; Protein Folding ; Protein Structure, Secondary ; Protein Structure, Tertiary
    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
  • 27
    facet.materialart.
    Unknown
    Cleanup crew (2015)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2015-03-07
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Leslie, Mitch -- New York, N.Y. -- Science. 2015 Mar 6;347(6226):1058-9, 1061. doi: 10.1126/science.347.6226.1058.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25745143" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antibodies, Monoclonal/chemistry/immunology/*therapeutic use ; Clinical Trials as Topic ; Drug Approval ; Humans ; Immune System/immunology ; Mice ; Multiple Sclerosis/*therapy ; Myelin Sheath/immunology ; Protein Conformation ; Recombinant Proteins/immunology/*therapeutic use ; United States ; United States Food and Drug Administration
    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
  • 28
    facet.materialart.
    Unknown
    Protein structure. Crystal structures of translocator protein (TSPO) and mutant mimic of a human polymorphism (2015)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2015-01-31
    Description: The 18-kilodalton translocator protein (TSPO), proposed to be a key player in cholesterol transport into mitochondria, is highly expressed in steroidogenic tissues, metastatic cancer, and inflammatory and neurological diseases such as Alzheimer's and Parkinson's. TSPO ligands, including benzodiazepine drugs, are implicated in regulating apoptosis and are extensively used in diagnostic imaging. We report crystal structures (at 1.8, 2.4, and 2.5 angstrom resolution) of TSPO from Rhodobacter sphaeroides and a mutant that mimics the human Ala(147)--〉Thr(147) polymorphism associated with psychiatric disorders and reduced pregnenolone production. Crystals obtained in the lipidic cubic phase reveal the binding site of an endogenous porphyrin ligand and conformational effects of the mutation. The three crystal structures show the same tightly interacting dimer and provide insights into the controversial physiological role of TSPO and how the mutation affects cholesterol binding.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Li, Fei -- Liu, Jian -- Zheng, Yi -- Garavito, R Michael -- Ferguson-Miller, Shelagh -- ACB-12002/PHS HHS/ -- AGM-12006/PHS HHS/ -- GM094625/GM/NIGMS NIH HHS/ -- GM26916/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2015 Jan 30;347(6221):555-8. doi: 10.1126/science.1260590.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI 48824, USA. ; Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI 48824, USA. fergus20@msu.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25635101" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Bacterial Proteins/*chemistry/*metabolism ; Binding Sites ; Cholesterol/metabolism ; Crystallography, X-Ray ; Humans ; Hydrogen Bonding ; Isoquinolines/metabolism ; Ligands ; Membrane Transport Proteins/*chemistry/*metabolism ; Models, Molecular ; Molecular Sequence Data ; Mutant Proteins/chemistry ; Polymorphism, Single Nucleotide ; Porphyrins/metabolism ; Protein Conformation ; Protein Multimerization ; Protein Structure, Secondary ; Protoporphyrins/metabolism ; Receptors, GABA/chemistry/genetics ; Rhodobacter sphaeroides/*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
  • 29
    facet.materialart.
    Unknown
    Cryo-EM shows the polymerase structures and a nonspooled genome within a dsRNA virus (2015)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2015-09-19
    Description: Double-stranded RNA (dsRNA) viruses possess a segmented dsRNA genome and a number of RNA-dependent RNA polymerases (RdRps) enclosed in a capsid. Until now, the precise structures of genomes and RdRps within the capsids have been unknown. Here we report the structures of RdRps and associated RNAs within nontranscribing and transcribing cypoviruses (NCPV and TCPV, respectively), using a combination of cryo-electron microscopy (cryo-EM) and a symmetry-mismatch reconstruction method. The RdRps and associated RNAs appear to exhibit a pseudo-D3 symmetric organization in both NCPV and TCPV. However, the molecular interactions between RdRps and the genomic RNA were found to differ in these states. Our work provides insight into the mechanisms of the replication and transcription in dsRNA viruses and paves a way for structural determination of lower-symmetry complexes enclosed in higher-symmetry structures.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Liu, Hongrong -- Cheng, Lingpeng -- New York, N.Y. -- Science. 2015 Sep 18;349(6254):1347-50. doi: 10.1126/science.aaa4938.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉College of Physics and Information Science, Hunan Normal University, Changsha, Hunan 410081, China. hrliu@hunnu.edu.cn lingpengcheng@mail.tsinghua.edu.cn. ; School of Life Sciences, Tsinghua University, Beijing 100084, China. hrliu@hunnu.edu.cn lingpengcheng@mail.tsinghua.edu.cn.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26383954" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Capsid/enzymology/ultrastructure ; Capsid Proteins/*ultrastructure ; Cryoelectron Microscopy ; Genome, Viral ; Humans ; Protein Conformation ; RNA Replicase/*ultrastructure ; RNA, Double-Stranded/genetics/*ultrastructure ; RNA, Viral/genetics/*ultrastructure ; *Reoviridae/enzymology/genetics/ultrastructure ; Transcription, Genetic ; 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
  • 30
    facet.materialart.
    Unknown
    Protein synthesis. Rqc2p and 60S ribosomal subunits mediate mRNA-independent elongation of nascent chains (2015)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2015-01-03
    Description: In Eukarya, stalled translation induces 40S dissociation and recruitment of the ribosome quality control complex (RQC) to the 60S subunit, which mediates nascent chain degradation. Here we report cryo-electron microscopy structures revealing that the RQC components Rqc2p (YPL009C/Tae2) and Ltn1p (YMR247C/Rkr1) bind to the 60S subunit at sites exposed after 40S dissociation, placing the Ltn1p RING (Really Interesting New Gene) domain near the exit channel and Rqc2p over the P-site transfer RNA (tRNA). We further demonstrate that Rqc2p recruits alanine- and threonine-charged tRNA to the A site and directs the elongation of nascent chains independently of mRNA or 40S subunits. Our work uncovers an unexpected mechanism of protein synthesis, in which a protein--not an mRNA--determines tRNA recruitment and the tagging of nascent chains with carboxy-terminal Ala and Thr extensions ("CAT tails").〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4451101/" 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/PMC4451101/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shen, Peter S -- Park, Joseph -- Qin, Yidan -- Li, Xueming -- Parsawar, Krishna -- Larson, Matthew H -- Cox, James -- Cheng, Yifan -- Lambowitz, Alan M -- Weissman, Jonathan S -- Brandman, Onn -- Frost, Adam -- 1DP2GM110772-01/DP/NCCDPHP CDC HHS/ -- DP2 GM110772/GM/NIGMS NIH HHS/ -- GM37949/GM/NIGMS NIH HHS/ -- GM37951/GM/NIGMS NIH HHS/ -- P50 GM102706/GM/NIGMS NIH HHS/ -- R01 GM037949/GM/NIGMS NIH HHS/ -- R01 GM037951/GM/NIGMS NIH HHS/ -- U01 GM098254/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2015 Jan 2;347(6217):75-8. doi: 10.1126/science.1259724.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, University of Utah, UT 84112, USA. ; Department of Biochemistry, Stanford University, Palo Alto, CA 94305, USA. ; Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, TX 78712, USA. Department of Molecular Biosciences, University of Texas at Austin, Austin, TX 78712, USA. ; Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA. ; Mass Spectrometry and Proteomics Core Facility, University of Utah, UT 84112, USA. ; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA. Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94158, USA. California Institute for Quantitative Biomedical Research, University of California, San Francisco, San Francisco, CA 94158, USA. Center for RNA Systems Biology, University of California, San Francisco, San Francisco, CA 94158, USA. ; Department of Biochemistry, University of Utah, UT 84112, USA. Mass Spectrometry and Proteomics Core Facility, University of Utah, UT 84112, USA. ; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA. Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94158, USA. California Institute for Quantitative Biomedical Research, University of California, San Francisco, San Francisco, CA 94158, USA. Center for RNA Systems Biology, University of California, San Francisco, San Francisco, CA 94158, USA. jonathan.weissman@ucsf.edu onn@stanford.edu adam.frost@ucsf.edu. ; Department of Biochemistry, Stanford University, Palo Alto, CA 94305, USA. jonathan.weissman@ucsf.edu onn@stanford.edu adam.frost@ucsf.edu. ; Department of Biochemistry, University of Utah, UT 84112, USA. Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA. jonathan.weissman@ucsf.edu onn@stanford.edu adam.frost@ucsf.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25554787" target="_blank"〉PubMed〈/a〉
    Keywords: Cryoelectron Microscopy ; Nucleic Acid Conformation ; *Peptide Biosynthesis, Nucleic Acid-Independent ; Protein Conformation ; RNA, Messenger/metabolism ; RNA, Transfer, Ala/chemistry/metabolism ; RNA, Transfer, Thr/chemistry/metabolism ; Ribosome Subunits, Large, Eukaryotic/chemistry/*metabolism/ultrastructure ; Saccharomyces cerevisiae/genetics/*metabolism ; Saccharomyces cerevisiae Proteins/*metabolism/ultrastructure ; Ubiquitin-Protein Ligases/*metabolism/ultrastructure
    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
  • 31
    facet.materialart.
    Unknown
    Structure of Tetrahymena telomerase reveals previously unknown subunits, functions, and interactions (2015)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2015-10-17
    Description: Telomerase helps maintain telomeres by processive synthesis of telomere repeat DNA at their 3'-ends, using an integral telomerase RNA (TER) and telomerase reverse transcriptase (TERT). We report the cryo-electron microscopy structure of Tetrahymena telomerase at ~9 angstrom resolution. In addition to seven known holoenzyme proteins, we identify two additional proteins that form a complex (TEB) with single-stranded telomere DNA-binding protein Teb1, paralogous to heterotrimeric replication protein A (RPA). The p75-p45-p19 subcomplex is identified as another RPA-related complex, CST (CTC1-STN1-TEN1). This study reveals the paths of TER in the TERT-TER-p65 catalytic core and single-stranded DNA exit; extensive subunit interactions of the TERT essential N-terminal domain, p50, and TEB; and other subunit identities and structures, including p19 and p45C crystal structures. Our findings provide structural and mechanistic insights into telomerase holoenzyme function.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4687456/" 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/PMC4687456/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jiang, Jiansen -- Chan, Henry -- Cash, Darian D -- Miracco, Edward J -- Ogorzalek Loo, Rachel R -- Upton, Heather E -- Cascio, Duilio -- O'Brien Johnson, Reid -- Collins, Kathleen -- Loo, Joseph A -- Zhou, Z Hong -- Feigon, Juli -- GM007185/GM/NIGMS NIH HHS/ -- GM048123/GM/NIGMS NIH HHS/ -- GM071940/GM/NIGMS NIH HHS/ -- GM101874/GM/NIGMS NIH HHS/ -- GM103479/GM/NIGMS NIH HHS/ -- P41 GM103403/GM/NIGMS NIH HHS/ -- P41 RR015301/RR/NCRR NIH HHS/ -- R01 GM048123/GM/NIGMS NIH HHS/ -- R01 GM054198/GM/NIGMS NIH HHS/ -- R01 GM071940/GM/NIGMS NIH HHS/ -- R01 GM103479/GM/NIGMS NIH HHS/ -- R01GM054198/GM/NIGMS NIH HHS/ -- S10OD018111/OD/NIH HHS/ -- S10RR23057/RR/NCRR NIH HHS/ -- UL1TR000124/TR/NCATS NIH HHS/ -- New York, N.Y. -- Science. 2015 Oct 30;350(6260):aab4070. doi: 10.1126/science.aab4070. Epub 2015 Oct 15.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry and Biochemistry, University of California, Los Angeles (UCLA), Los Angeles, CA 90095, USA. Department of Microbiology, Immunology, and Molecular Genetics, UCLA, Los Angeles, CA 90095, USA. California Nanosystems Institute, UCLA, Los Angeles, CA 90095, USA. ; Department of Chemistry and Biochemistry, University of California, Los Angeles (UCLA), Los Angeles, CA 90095, USA. ; Department of Biological Chemistry, UCLA, Los Angeles, CA 90095, USA. ; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA. ; Department of Chemistry and Biochemistry, University of California, Los Angeles (UCLA), Los Angeles, CA 90095, USA. UCLA-U.S. Department of Energy (DOE) Institute of Genomics and Proteomics, UCLA, Los Angeles, CA 90095, USA. ; Department of Chemistry and Biochemistry, University of California, Los Angeles (UCLA), Los Angeles, CA 90095, USA. Department of Biological Chemistry, UCLA, Los Angeles, CA 90095, USA. UCLA-U.S. Department of Energy (DOE) Institute of Genomics and Proteomics, UCLA, Los Angeles, CA 90095, USA. ; Department of Microbiology, Immunology, and Molecular Genetics, UCLA, Los Angeles, CA 90095, USA. California Nanosystems Institute, UCLA, Los Angeles, CA 90095, USA. ; Department of Chemistry and Biochemistry, University of California, Los Angeles (UCLA), Los Angeles, CA 90095, USA. California Nanosystems Institute, UCLA, Los Angeles, CA 90095, USA. UCLA-U.S. Department of Energy (DOE) Institute of Genomics and Proteomics, UCLA, Los Angeles, CA 90095, USA. feigon@mbi.ucla.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26472759" target="_blank"〉PubMed〈/a〉
    Keywords: Catalytic Domain ; Cryoelectron Microscopy ; Crystallography, X-Ray ; DNA, Single-Stranded/chemistry ; Holoenzymes/chemistry ; Protein Binding ; Protein Conformation ; Protein Subunits/chemistry ; RNA/*chemistry ; Replication Protein A/chemistry ; Telomerase/*chemistry ; Telomere/chemistry ; Telomere Homeostasis ; Telomere-Binding Proteins ; Tetrahymena/*enzymology
    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
  • 32
    facet.materialart.
    Unknown
    Proteasomes. A molecular census of 26S proteasomes in intact neurons (2015)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2015-01-24
    Description: The 26S proteasome is a key player in eukaryotic protein quality control and in the regulation of numerous cellular processes. Here, we describe quantitative in situ structural studies of this highly dynamic molecular machine in intact hippocampal neurons. We used electron cryotomography with the Volta phase plate, which allowed high fidelity and nanometer precision localization of 26S proteasomes. We undertook a molecular census of single- and double-capped proteasomes and assessed the conformational states of individual complexes. Under the conditions of the experiment-that is, in the absence of proteotoxic stress-only 20% of the 26S proteasomes were engaged in substrate processing. The remainder was in the substrate-accepting ground state. These findings suggest that in the absence of stress, the capacity of the proteasome system is not fully used.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Asano, Shoh -- Fukuda, Yoshiyuki -- Beck, Florian -- Aufderheide, Antje -- Forster, Friedrich -- Danev, Radostin -- Baumeister, Wolfgang -- New York, N.Y. -- Science. 2015 Jan 23;347(6220):439-42. doi: 10.1126/science.1261197.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Structural Biology, Max-Planck Institute of Biochemistry, 82152 Martinsried, Germany. ; Department of Molecular Structural Biology, Max-Planck Institute of Biochemistry, 82152 Martinsried, Germany. baumeist@biochem.mpg.de.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25613890" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cells, Cultured ; Hippocampus/*cytology/enzymology ; Neurons/*enzymology/*ultrastructure ; Proteasome Endopeptidase Complex/*chemistry ; Protein Conformation ; Rats ; Stress, Physiological
    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
  • 33
    facet.materialart.
    Unknown
    Protein structure. Engineering of a superhelicase through conformational control (2015)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2015-04-18
    Description: Conformational control of biomolecular activities can reveal functional insights and enable the engineering of novel activities. Here we show that conformational control through intramolecular cross-linking of a helicase monomer with undetectable unwinding activity converts it into a superhelicase that can unwind thousands of base pairs processively, even against a large opposing force. A natural partner that enhances the helicase activity is shown to achieve its stimulating role also by selectively stabilizing the active conformation. Our work provides insight into the regulation of nucleic acid unwinding activity and introduces a monomeric superhelicase without nuclease activities, which may be useful for biotechnological applications.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4417355/" 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/PMC4417355/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Arslan, Sinan -- Khafizov, Rustem -- Thomas, Christopher D -- Chemla, Yann R -- Ha, Taekjip -- GM065367/GM/NIGMS NIH HHS/ -- R01 GM065367/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2015 Apr 17;348(6232):344-7. doi: 10.1126/science.aaa0445.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Physics Department and Center for the Physics of Living Cells, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA. ; Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds LS2 9JT, UK. ; Physics Department and Center for the Physics of Living Cells, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA. Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA. Howard Hughes Medical Institute, University of Illinois, Urbana, IL 61801, USA. tjha@illinois.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25883358" target="_blank"〉PubMed〈/a〉
    Keywords: Bacterial Proteins/*chemistry/genetics ; Cross-Linking Reagents/chemistry ; Crystallography, X-Ray ; DNA Helicases/*chemistry/genetics ; *DNA Replication ; DNA, Single-Stranded/*chemistry ; Deoxyribonucleases/chemistry/genetics ; Enzyme Stability ; Escherichia coli Proteins/*chemistry/genetics ; Protein Conformation ; Protein Engineering
    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
  • 34
    facet.materialart.
    Unknown
    Protein structure. Direct observation of structure-function relationship in a nucleic acid-processing enzyme (2015)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2015-04-18
    Description: The relationship between protein three-dimensional structure and function is essential for mechanism determination. Unfortunately, most techniques do not provide a direct measurement of this relationship. Structural data are typically limited to static pictures, and function must be inferred. Conversely, functional assays usually provide little information on structural conformation. We developed a single-molecule technique combining optical tweezers and fluorescence microscopy that allows for both measurements simultaneously. Here we present measurements of UvrD, a DNA repair helicase, that directly and unambiguously reveal the connection between its structure and function. Our data reveal that UvrD exhibits two distinct types of unwinding activity regulated by its stoichiometry. Furthermore, two UvrD conformational states, termed "closed" and "open," correlate with movement toward or away from the DNA fork.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4424897/" 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/PMC4424897/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Comstock, Matthew J -- Whitley, Kevin D -- Jia, Haifeng -- Sokoloski, Joshua -- Lohman, Timothy M -- Ha, Taekjip -- Chemla, Yann R -- R01 GM045948/GM/NIGMS NIH HHS/ -- R01 GM065367/GM/NIGMS NIH HHS/ -- R21 RR025341/RR/NCRR NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2015 Apr 17;348(6232):352-4. doi: 10.1126/science.aaa0130. Epub 2015 Apr 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physics, Center for the Physics of Living Cells, and Center for Biophysics and Computational Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA. ; Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, MO 63110, USA. ; Department of Physics, Center for the Physics of Living Cells, and Center for Biophysics and Computational Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA. Howard Hughes Medical Institute, Urbana, IL 61801, USA. Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA. ; Department of Physics, Center for the Physics of Living Cells, and Center for Biophysics and Computational Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA. ychemla@illinois.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25883359" target="_blank"〉PubMed〈/a〉
    Keywords: DNA Helicases/*chemistry/*physiology ; DNA Repair ; *DNA Replication ; Escherichia coli Proteins/*chemistry/*physiology ; Microscopy, Fluorescence/methods ; Optical Tweezers ; Protein Conformation ; Structure-Activity Relationship
    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
  • 35
    facet.materialart.
    Unknown
    TRANSCRIPTION. Structures of the RNA polymerase-sigma54 reveal new and conserved regulatory strategies (2015)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2015-08-22
    Description: Transcription by RNA polymerase (RNAP) in bacteria requires specific promoter recognition by sigma factors. The major variant sigma factor (sigma(54)) initially forms a transcriptionally silent complex requiring specialized adenosine triphosphate-dependent activators for initiation. Our crystal structure of the 450-kilodalton RNAP-sigma(54) holoenzyme at 3.8 angstroms reveals molecular details of sigma(54) and its interactions with RNAP. The structure explains how sigma(54) targets different regions in RNAP to exert its inhibitory function. Although sigma(54) and the major sigma factor, sigma(70), have similar functional domains and contact similar regions of RNAP, unanticipated differences are observed in their domain arrangement and interactions with RNAP, explaining their distinct properties. Furthermore, we observe evolutionarily conserved regulatory hotspots in RNAPs that can be targeted by a diverse range of mechanisms to fine tune transcription.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4681505/" 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/PMC4681505/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yang, Yun -- Darbari, Vidya C -- Zhang, Nan -- Lu, Duo -- Glyde, Robert -- Wang, Yi-Ping -- Winkelman, Jared T -- Gourse, Richard L -- Murakami, Katsuhiko S -- Buck, Martin -- Zhang, Xiaodong -- 098412/Wellcome Trust/United Kingdom -- BB/C504700/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- GM087350/GM/NIGMS NIH HHS/ -- R01 GM087350/GM/NIGMS NIH HHS/ -- R37 GM37048/GM/NIGMS NIH HHS/ -- Biotechnology and Biological Sciences Research Council/United Kingdom -- New York, N.Y. -- Science. 2015 Aug 21;349(6250):882-5. doi: 10.1126/science.aab1478.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Centre for Structural Biology, Imperial College London, South Kensington SW7 2AZ, UK. State Key Laboratory of Protein and Plant Gene Research, College of Life Sciences, Peking University, China. ; Centre for Structural Biology, Imperial College London, South Kensington SW7 2AZ, UK. Department of Medicine, Imperial College London, South Kensington SW7 2AZ, UK. ; Department of Life Sciences, Imperial College London, South Kensington SW7 2AZ, UK. ; Centre for Structural Biology, Imperial College London, South Kensington SW7 2AZ, UK. ; State Key Laboratory of Protein and Plant Gene Research, College of Life Sciences, Peking University, China. ; Department of Bacteriology, University of Wisconsin, Madison, WI 53706, USA. ; Department of Biochemistry and Molecular Biology, Center for RNA Molecular Biology, Pennsylvania State University, University Park, PA 16802, USA. ; Centre for Structural Biology, Imperial College London, South Kensington SW7 2AZ, UK. Department of Medicine, Imperial College London, South Kensington SW7 2AZ, UK. xiaodong.zhang@imperial.ac.uk.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26293966" target="_blank"〉PubMed〈/a〉
    Keywords: Crystallography, X-Ray ; Enzyme Stability ; *Evolution, Molecular ; *Gene Expression Regulation ; Holoenzymes/chemistry ; Protein Conformation ; Protein Structure, Tertiary ; RNA Polymerase Sigma 54/*chemistry/genetics ; *Transcription, Genetic
    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
  • 36
    facet.materialart.
    Unknown
    Protein structure. Structure and activity of tryptophan-rich TSPO proteins (2015)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2015-01-31
    Description: Translocator proteins (TSPOs) bind steroids and porphyrins, and they are implicated in many human diseases, for which they serve as biomarkers and therapeutic targets. TSPOs have tryptophan-rich sequences that are highly conserved from bacteria to mammals. Here we report crystal structures for Bacillus cereus TSPO (BcTSPO) down to 1.7 A resolution, including a complex with the benzodiazepine-like inhibitor PK11195. We also describe BcTSPO-mediated protoporphyrin IX (PpIX) reactions, including catalytic degradation to a previously undescribed heme derivative. We used structure-inspired mutations to investigate reaction mechanisms, and we showed that TSPOs from Xenopus and man have similar PpIX-directed activities. Although TSPOs have been regarded as transporters, the catalytic activity in PpIX degradation suggests physiological importance for TSPOs in protection against oxidative stress.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4341906/" 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/PMC4341906/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Guo, Youzhong -- Kalathur, Ravi C -- Liu, Qun -- Kloss, Brian -- Bruni, Renato -- Ginter, Christopher -- Kloppmann, Edda -- Rost, Burkhard -- Hendrickson, Wayne A -- GM095315/GM/NIGMS NIH HHS/ -- GM107462/GM/NIGMS NIH HHS/ -- R01 GM107462/GM/NIGMS NIH HHS/ -- U54 GM075026/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2015 Jan 30;347(6221):551-5. doi: 10.1126/science.aaa1534.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA. ; The New York Consortium on Membrane Protein Structure (NYCOMPS), New York Structural Biology Center, 89 Convent Avenue, New York, NY 10027, USA. ; The New York Consortium on Membrane Protein Structure (NYCOMPS), New York Structural Biology Center, 89 Convent Avenue, New York, NY 10027, USA. New York Structural Biology Center, Synchrotron Beamlines, Brookhaven National Laboratory, Upton, NY 11973, USA. ; The New York Consortium on Membrane Protein Structure (NYCOMPS), New York Structural Biology Center, 89 Convent Avenue, New York, NY 10027, USA. Department of Informatics, Bioinformatics and Computational Biology, Technische Universitat Munchen, Garching 85748, Germany. ; Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA. The New York Consortium on Membrane Protein Structure (NYCOMPS), New York Structural Biology Center, 89 Convent Avenue, New York, NY 10027, USA. New York Structural Biology Center, Synchrotron Beamlines, Brookhaven National Laboratory, Upton, NY 11973, USA. Department of Physiology and Cellular Biophysics, Columbia University, New York, NY 10032, USA. wayne@xtl.cumc.columbia.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25635100" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Bacillus cereus/*chemistry ; Bacterial Proteins/*chemistry/*metabolism ; Binding Sites ; Crystallography, X-Ray ; Isoquinolines/metabolism ; Ligands ; Membrane Transport Proteins/*chemistry/*metabolism ; Molecular Sequence Data ; Mutant Proteins/chemistry/metabolism ; Protein Conformation ; Protein Multimerization ; Protein Structure, Secondary ; Protein Subunits/chemistry ; Protoporphyrins/metabolism ; Reactive Oxygen Species/metabolism ; Tryptophan/analysis
    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
  • 37
    facet.materialart.
    Unknown
    Rationally engineered Cas9 nucleases with improved specificity (2015)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2015-12-03
    Description: The RNA-guided endonuclease Cas9 is a versatile genome-editing tool with a broad range of applications from therapeutics to functional annotation of genes. Cas9 creates double-strand breaks (DSBs) at targeted genomic loci complementary to a short RNA guide. However, Cas9 can cleave off-target sites that are not fully complementary to the guide, which poses a major challenge for genome editing. Here, we use structure-guided protein engineering to improve the specificity of Streptococcus pyogenes Cas9 (SpCas9). Using targeted deep sequencing and unbiased whole-genome off-target analysis to assess Cas9-mediated DNA cleavage in human cells, we demonstrate that "enhanced specificity" SpCas9 (eSpCas9) variants reduce off-target effects and maintain robust on-target cleavage. Thus, eSpCas9 could be broadly useful for genome-editing applications requiring a high level of specificity.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4714946/" 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/PMC4714946/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Slaymaker, Ian M -- Gao, Linyi -- Zetsche, Bernd -- Scott, David A -- Yan, Winston X -- Zhang, Feng -- 1R01MH110049/MH/NIMH NIH HHS/ -- 5DP1-MH100706/DP/NCCDPHP CDC HHS/ -- 5R01DK097768-03/DK/NIDDK NIH HHS/ -- DP1 MH100706/MH/NIMH NIH HHS/ -- T32GM007753/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2016 Jan 1;351(6268):84-8. doi: 10.1126/science.aad5227. Epub 2015 Dec 1.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. ; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. ; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Graduate Program in Biophysics, Harvard Medical School, Boston, MA 02115, USA. Harvard-MIT Division of Health Sciences and Technology, Harvard Medical School, Boston, MA 02115, USA. ; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. zhang@broadinstitute.org.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26628643" target="_blank"〉PubMed〈/a〉
    Keywords: Bacterial Proteins/*chemistry/genetics ; *DNA Cleavage ; Endonucleases/*chemistry/genetics ; Humans ; Mutagenesis ; Point Mutation ; Protein Conformation ; *Protein Engineering ; RNA, Guide/genetics ; Streptococcus pyogenes/*enzymology
    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
  • 38
    facet.materialart.
    Unknown
    Replisome speed determines the efficiency of the Tus-Ter replication termination barrier (2015)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2015-09-01
    Description: In all domains of life, DNA synthesis occurs bidirectionally from replication origins. Despite variable rates of replication fork progression, fork convergence often occurs at specific sites. Escherichia coli sets a 'replication fork trap' that allows the first arriving fork to enter but not to leave the terminus region. The trap is set by oppositely oriented Tus-bound Ter sites that block forks on approach from only one direction. However, the efficiency of fork blockage by Tus-Ter does not exceed 50% in vivo despite its apparent ability to almost permanently arrest replication forks in vitro. Here we use data from single-molecule DNA replication assays and structural studies to show that both polarity and fork-arrest efficiency are determined by a competition between rates of Tus displacement and rearrangement of Tus-Ter interactions that leads to blockage of slower moving replisomes by two distinct mechanisms. To our knowledge this is the first example where intrinsic differences in rates of individual replisomes have different biological outcomes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Elshenawy, Mohamed M -- Jergic, Slobodan -- Xu, Zhi-Qiang -- Sobhy, Mohamed A -- Takahashi, Masateru -- Oakley, Aaron J -- Dixon, Nicholas E -- Hamdan, Samir M -- England -- Nature. 2015 Sep 17;525(7569):394-8. doi: 10.1038/nature14866. Epub 2015 Aug 31.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Biological and Environmental Sciences and Engineering, King Abdullah University of Science and Technology, Thuwal 23955, Saudi Arabia. ; Centre for Medical &Molecular Bioscience, Illawarra Health &Medical Research Institute and University of Wollongong, New South Wales 2522, Australia.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26322585" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; Binding, Competitive ; Chromosomes, Bacterial/genetics/metabolism ; Crystallography, X-Ray ; *DNA Replication ; DNA-Directed DNA Polymerase/chemistry/*metabolism ; Escherichia coli/*genetics/metabolism ; Escherichia coli Proteins/chemistry/*metabolism ; Kinetics ; Models, Biological ; Models, Molecular ; Movement ; Multienzyme Complexes/chemistry/*metabolism ; Protein Conformation ; Regulatory Sequences, Nucleic Acid/*genetics ; Surface Plasmon Resonance ; 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
  • 39
    facet.materialart.
    Unknown
    Recognition determinants of broadly neutralizing human antibodies against dengue viruses (2015)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2015-01-13
    Description: Dengue disease is caused by four different flavivirus serotypes, which infect 390 million people yearly with 25% symptomatic cases and for which no licensed vaccine is available. Recent phase III vaccine trials showed partial protection, and in particular no protection for dengue virus serotype 2 (refs 3, 4). Structural studies so far have characterized only epitopes recognized by serotype-specific human antibodies. We recently isolated human antibodies potently neutralizing all four dengue virus serotypes. Here we describe the X-ray structures of four of these broadly neutralizing antibodies in complex with the envelope glycoprotein E from dengue virus serotype 2, revealing that the recognition determinants are at a serotype-invariant site at the E-dimer interface, including the exposed main chain of the E fusion loop and the two conserved glycan chains. This 'E-dimer-dependent epitope' is also the binding site for the viral glycoprotein prM during virus maturation in the secretory pathway of the infected cell, explaining its conservation across serotypes and highlighting an Achilles' heel of the virus with respect to antibody neutralization. These findings will be instrumental for devising novel immunogens to protect simultaneously against all four serotypes of dengue virus.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rouvinski, Alexander -- Guardado-Calvo, Pablo -- Barba-Spaeth, Giovanna -- Duquerroy, Stephane -- Vaney, Marie-Christine -- Kikuti, Carlos M -- Navarro Sanchez, M Erika -- Dejnirattisai, Wanwisa -- Wongwiwat, Wiyada -- Haouz, Ahmed -- Girard-Blanc, Christine -- Petres, Stephane -- Shepard, William E -- Despres, Philippe -- Arenzana-Seisdedos, Fernando -- Dussart, Philippe -- Mongkolsapaya, Juthathip -- Screaton, Gavin R -- Rey, Felix A -- 095541/Wellcome Trust/United Kingdom -- Medical Research Council/United Kingdom -- Wellcome Trust/United Kingdom -- England -- Nature. 2015 Apr 2;520(7545):109-13. doi: 10.1038/nature14130. Epub 2015 Jan 12.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Institut Pasteur, Departement de Virologie, Unite de Virologie Structurale, 75724 Paris Cedex 15, France [2] CNRS UMR 3569 Virologie, 75724 Paris Cedex 15, France. ; 1] Institut Pasteur, Departement de Virologie, Unite de Virologie Structurale, 75724 Paris Cedex 15, France [2] CNRS UMR 3569 Virologie, 75724 Paris Cedex 15, France [3] Universite Paris-Sud, Faculte des Sciences, 91405 Orsay, France. ; Division of Immunology and Inflammation, Department of Medicine, Hammersmith Hospital Campus, Imperial College London, London W12 0NN, UK. ; Institut Pasteur, Proteopole, CNRS UMR 3528, 75724 Paris Cedex 15, France. ; Synchrotron SOLEIL, L'Orme des Merisiers, Saint Aubin, BP48, 91192 Gif-sur-Yvette, France. ; Institut Pasteur, Departement de Virologie, Unite des Interactions Moleculaires Flavivirus-Hotes, 75724 Paris Cedex 15, France. ; Institut Pasteur, Departement de Virologie, Unite de Pathogenie Virale, INSERM U1108, 75724 Paris Cedex 15, France. ; Institut Pasteur de Guyane, BP 6010, 97306 Cayenne, French Guiana. ; 1] Division of Immunology and Inflammation, Department of Medicine, Hammersmith Hospital Campus, Imperial College London, London W12 0NN, UK [2] Dengue Hemorrhagic Fever Research Unit, Office for Research and Development, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand. ; 1] Institut Pasteur, Departement de Virologie, Unite de Virologie Structurale, 75724 Paris Cedex 15, France [2] CNRS UMR 3569 Virologie, 75724 Paris Cedex 15, France [3] Institut Pasteur, Proteopole, CNRS UMR 3528, 75724 Paris Cedex 15, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25581790" target="_blank"〉PubMed〈/a〉
    Keywords: Antibodies, Neutralizing/*chemistry/genetics/*immunology ; Antibodies, Viral/*chemistry/genetics/*immunology ; Cross Reactions/immunology ; Crystallography, X-Ray ; Dengue Virus/*chemistry/classification/*immunology ; Epitopes/chemistry/immunology ; Humans ; Models, Molecular ; Molecular Sequence Data ; Mutation/genetics ; Protein Conformation ; Protein Multimerization ; Solubility ; Species Specificity ; Viral Envelope Proteins/chemistry/immunology
    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
    Atomic structure of anthrax protective antigen pore elucidates toxin translocation (2015)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2015-03-18
    Description: Anthrax toxin, comprising protective antigen, lethal factor, and oedema factor, is the major virulence factor of Bacillus anthracis, an agent that causes high mortality in humans and animals. Protective antigen forms oligomeric prepores that undergo conversion to membrane-spanning pores by endosomal acidification, and these pores translocate the enzymes lethal factor and oedema factor into the cytosol of target cells. Protective antigen is not only a vaccine component and therapeutic target for anthrax infections but also an excellent model system for understanding the mechanism of protein translocation. On the basis of biochemical and electrophysiological results, researchers have proposed that a phi (Phi)-clamp composed of phenylalanine (Phe)427 residues of protective antigen catalyses protein translocation via a charge-state-dependent Brownian ratchet. Although atomic structures of protective antigen prepores are available, how protective antigen senses low pH, converts to active pore, and translocates lethal factor and oedema factor are not well defined without an atomic model of its pore. Here, by cryo-electron microscopy with direct electron counting, we determine the protective antigen pore structure at 2.9-A resolution. The structure reveals the long-sought-after catalytic Phi-clamp and the membrane-spanning translocation channel, and supports the Brownian ratchet model for protein translocation. Comparisons of four structures reveal conformational changes in prepore to pore conversion that support a multi-step mechanism by which low pH is sensed and the membrane-spanning channel is formed.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4519040/" 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/PMC4519040/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jiang, Jiansen -- Pentelute, Bradley L -- Collier, R John -- Zhou, Z Hong -- 1S10OD018111/OD/NIH HHS/ -- 1S10RR23057/RR/NCRR NIH HHS/ -- AI022021/AI/NIAID NIH HHS/ -- AI046420/AI/NIAID NIH HHS/ -- AI057159/AI/NIAID NIH HHS/ -- AI094386/AI/NIAID NIH HHS/ -- GM071940/GM/NIGMS NIH HHS/ -- R01 AI094386/AI/NIAID NIH HHS/ -- R01 GM071940/GM/NIGMS NIH HHS/ -- S10 OD018111/OD/NIH HHS/ -- S10 RR023057/RR/NCRR NIH HHS/ -- England -- Nature. 2015 May 28;521(7553):545-9. doi: 10.1038/nature14247. Epub 2015 Mar 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, California 90095, USA [2] California NanoSystems Institute, University of California, Los Angeles, California 90095, USA. ; Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA. ; Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25778700" target="_blank"〉PubMed〈/a〉
    Keywords: Antigens, Bacterial/chemistry/*metabolism/*ultrastructure ; Bacillus anthracis/*chemistry/*ultrastructure ; Bacterial Toxins/chemistry/*metabolism ; Biocatalysis ; *Cryoelectron Microscopy ; Hydrogen-Ion Concentration ; Ion Channels/chemistry/metabolism/ultrastructure ; Models, Molecular ; Phenylalanine/metabolism ; Protein Conformation ; Protein Transport ; 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
  • 41
    facet.materialart.
    Unknown
    Structural basis for stop codon recognition in eukaryotes (2015)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2015-08-08
    Description: Termination of protein synthesis occurs when a translating ribosome encounters one of three universally conserved stop codons: UAA, UAG or UGA. Release factors recognize stop codons in the ribosomal A-site to mediate release of the nascent chain and recycling of the ribosome. Bacteria decode stop codons using two separate release factors with differing specificities for the second and third bases. By contrast, eukaryotes rely on an evolutionarily unrelated omnipotent release factor (eRF1) to recognize all three stop codons. The molecular basis of eRF1 discrimination for stop codons over sense codons is not known. Here we present cryo-electron microscopy (cryo-EM) structures at 3.5-3.8 A resolution of mammalian ribosomal complexes containing eRF1 interacting with each of the three stop codons in the A-site. Binding of eRF1 flips nucleotide A1825 of 18S ribosomal RNA so that it stacks on the second and third stop codon bases. This configuration pulls the fourth position base into the A-site, where it is stabilized by stacking against G626 of 18S rRNA. Thus, eRF1 exploits two rRNA nucleotides also used during transfer RNA selection to drive messenger RNA compaction. In this compacted mRNA conformation, stop codons are favoured by a hydrogen-bonding network formed between rRNA and essential eRF1 residues that constrains the identity of the bases. These results provide a molecular framework for eukaryotic stop codon recognition and have implications for future studies on the mechanisms of canonical and premature translation termination.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4591471/" 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/PMC4591471/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Brown, Alan -- Shao, Sichen -- Murray, Jason -- Hegde, Ramanujan S -- Ramakrishnan, V -- 096570/Wellcome Trust/United Kingdom -- MC_U105184332/Medical Research Council/United Kingdom -- MC_UP_A022_1007/Medical Research Council/United Kingdom -- WT096570/Wellcome Trust/United Kingdom -- England -- Nature. 2015 Aug 27;524(7566):493-6. doi: 10.1038/nature14896. Epub 2015 Aug 5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26245381" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Motifs ; Binding Sites ; Codon/chemistry/genetics/metabolism ; Codon, Terminator/*chemistry/genetics/*metabolism ; Cryoelectron Microscopy ; Eukaryota ; Humans ; Hydrogen Bonding ; Models, Molecular ; Nucleic Acid Conformation ; Nucleotides/chemistry/metabolism ; Peptide Termination Factors/*chemistry/*metabolism ; Protein Biosynthesis ; Protein Conformation ; RNA, Messenger/chemistry/genetics/metabolism ; RNA, Ribosomal, 18S/genetics ; Ribosomes/chemistry/metabolism ; 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
  • 42
    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
  • 43
    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
  • 44
    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
  • 45
    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
  • 46
    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
  • 47
    facet.materialart.
    Unknown
    Conversion of channelrhodopsin into a light-gated chloride channel (2014)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2014-03-29
    Description: The field of optogenetics uses channelrhodopsins (ChRs) for light-induced neuronal activation. However, optimized tools for cellular inhibition at moderate light levels are lacking. We found that replacement of E90 in the central gate of ChR with positively charged residues produces chloride-conducting ChRs (ChloCs) with only negligible cation conductance. Molecular dynamics modeling unveiled that a high-affinity Cl(-)-binding site had been generated near the gate. Stabilizing the open state dramatically increased the operational light sensitivity of expressing cells (slow ChloC). In CA1 pyramidal cells, ChloCs completely inhibited action potentials triggered by depolarizing current injections or synaptic stimulation. Thus, by inverting the charge of the selectivity filter, we have created a class of directly light-gated anion channels that can be used to block neuronal output in a fully reversible fashion.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wietek, Jonas -- Wiegert, J Simon -- Adeishvili, Nona -- Schneider, Franziska -- Watanabe, Hiroshi -- Tsunoda, Satoshi P -- Vogt, Arend -- Elstner, Marcus -- Oertner, Thomas G -- Hegemann, Peter -- New York, N.Y. -- Science. 2014 Apr 25;344(6182):409-12. doi: 10.1126/science.1249375. Epub 2014 Mar 27.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute for Biology, Experimental Biophysics, Humboldt Universitat zu Berlin, D-10115 Berlin, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24674867" target="_blank"〉PubMed〈/a〉
    Keywords: Action Potentials ; Animals ; Binding Sites ; CA1 Region, Hippocampal/cytology ; Chloride Channels/*chemistry/*metabolism ; Chlorides/*metabolism ; HEK293 Cells ; Humans ; Hydrogen Bonding ; Ion Channel Gating ; Light ; Models, Molecular ; Molecular Dynamics Simulation ; Mutation ; Patch-Clamp Techniques ; Protein Conformation ; Protein Engineering ; Pyramidal Cells/metabolism ; Rats ; Recombinant Fusion Proteins/chemistry ; Rhodopsin/*chemistry/genetics/*metabolism ; Transfection
    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
  • 48
    facet.materialart.
    Unknown
    Structure of a class C GPCR metabotropic glutamate receptor 1 bound to an allosteric modulator (2014)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2014-03-08
    Description: The excitatory neurotransmitter glutamate induces modulatory actions via the metabotropic glutamate receptors (mGlus), which are class C G protein-coupled receptors (GPCRs). We determined the structure of the human mGlu1 receptor seven-transmembrane (7TM) domain bound to a negative allosteric modulator, FITM, at a resolution of 2.8 angstroms. The modulator binding site partially overlaps with the orthosteric binding sites of class A GPCRs but is more restricted than most other GPCRs. We observed a parallel 7TM dimer mediated by cholesterols, which suggests that signaling initiated by glutamate's interaction with the extracellular domain might be mediated via 7TM interactions within the full-length receptor dimer. A combination of crystallography, structure-activity relationships, mutagenesis, and full-length dimer modeling provides insights about the allosteric modulation and activation mechanism of class C GPCRs.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3991565/" 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/PMC3991565/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wu, Huixian -- Wang, Chong -- Gregory, Karen J -- Han, Gye Won -- Cho, Hyekyung P -- Xia, Yan -- Niswender, Colleen M -- Katritch, Vsevolod -- Meiler, Jens -- Cherezov, Vadim -- Conn, P Jeffrey -- Stevens, Raymond C -- P50 GM073197/GM/NIGMS NIH HHS/ -- R01 DK097376/DK/NIDDK NIH HHS/ -- R01 GM080403/GM/NIGMS NIH HHS/ -- R01 GM099842/GM/NIGMS NIH HHS/ -- R01 MH062646/MH/NIMH NIH HHS/ -- R01 MH090192/MH/NIMH NIH HHS/ -- R01 NS031373/NS/NINDS NIH HHS/ -- R21 NS078262/NS/NINDS NIH HHS/ -- R37 NS031373/NS/NINDS NIH HHS/ -- U54 GM094618/GM/NIGMS NIH HHS/ -- Y1-CO-1020/CO/NCI NIH HHS/ -- Y1-GM-1104/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2014 Apr 4;344(6179):58-64. doi: 10.1126/science.1249489. Epub 2014 Mar 6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Integrative Structural and Computational Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24603153" target="_blank"〉PubMed〈/a〉
    Keywords: Allosteric Regulation ; Allosteric Site ; Amino Acid Sequence ; Benzamides/*chemistry/*metabolism ; Binding Sites ; Cholesterol ; Crystallography, X-Ray ; Humans ; Hydrophobic and Hydrophilic Interactions ; Ligands ; Models, Molecular ; Molecular Sequence Data ; Mutation ; Protein Conformation ; Protein Multimerization ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Receptors, Metabotropic Glutamate/*chemistry/*metabolism ; Structure-Activity Relationship ; Thiazoles/*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
  • 49
    facet.materialart.
    Unknown
    Cryo-EM study of the chromatin fiber reveals a double helix twisted by tetranucleosomal units (2014)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2014-04-26
    Description: The hierarchical packaging of eukaryotic chromatin plays a central role in transcriptional regulation and other DNA-related biological processes. Here, we report the 11-angstrom-resolution cryogenic electron microscopy (cryo-EM) structures of 30-nanometer chromatin fibers reconstituted in the presence of linker histone H1 and with different nucleosome repeat lengths. The structures show a histone H1-dependent left-handed twist of the repeating tetranucleosomal structural units, within which the four nucleosomes zigzag back and forth with a straight linker DNA. The asymmetric binding and the location of histone H1 in chromatin play a role in the formation of the 30-nanometer fiber. Our results provide mechanistic insights into how nucleosomes compact into higher-order chromatin fibers.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Song, Feng -- Chen, Ping -- Sun, Dapeng -- Wang, Mingzhu -- Dong, Liping -- Liang, Dan -- Xu, Rui-Ming -- Zhu, Ping -- Li, Guohong -- New York, N.Y. -- Science. 2014 Apr 25;344(6182):376-80. doi: 10.1126/science.1251413.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24763583" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Chromatin/chemistry/metabolism/*ultrastructure ; Cryoelectron Microscopy ; DNA/chemistry/*ultrastructure ; Histones/*chemistry/metabolism ; Imaging, Three-Dimensional ; Models, Molecular ; Molecular Sequence Data ; Nucleic Acid Conformation ; Nucleosomes/*ultrastructure ; Protein Conformation ; Recombinant Proteins/chemistry/metabolism ; Xenopus Proteins/chemistry ; Xenopus laevis
    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
  • 50
    facet.materialart.
    Unknown
    Structures of bacterial homologues of SWEET transporters in two distinct conformations (2014)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2014-09-05
    Description: SWEETs and their prokaryotic homologues are monosaccharide and disaccharide transporters that are present from Archaea to plants and humans. SWEETs play crucial roles in cellular sugar efflux processes: that is, in phloem loading, pollen nutrition and nectar secretion. Their bacterial homologues, which are called SemiSWEETs, are among the smallest known transporters. Here we show that SemiSWEET molecules, which consist of a triple-helix bundle, form symmetrical, parallel dimers, thereby generating the translocation pathway. Two SemiSWEET isoforms were crystallized, one in an apparently open state and one in an occluded state, indicating that SemiSWEETs and SWEETs are transporters that undergo rocking-type movements during the transport cycle. The topology of the triple-helix bundle is similar yet distinct to that of the basic building block of animal and plant major facilitator superfamily (MFS) transporters (for example, GLUTs and SUTs). This finding indicates two possibilities: that SWEETs and MFS transporters evolved from an ancestral triple-helix bundle or that the triple-helix bundle represents convergent evolution. In SemiSWEETs and SWEETs, two triple-helix bundles are arranged in a parallel configuration to produce the 6- and 6 + 1-transmembrane-helix pores, respectively. In the 12-transmembrane-helix MFS transporters, four triple-helix bundles are arranged into an alternating antiparallel configuration, resulting in a much larger 2 x 2 triple-helix bundle forming the pore. Given the similarity of SemiSWEETs and SWEETs to PQ-loop amino acid transporters and to mitochondrial pyruvate carriers (MPCs), the structures characterized here may also be relevant to other transporters in the MtN3 clan. The insight gained from the structures of these transporters and from the analysis of mutations of conserved residues will improve the understanding of the transport mechanism, as well as allow comparative studies of the different superfamilies involved in sugar transport and the evolution of transporters in general.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4300204/" 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/PMC4300204/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Xu, Yan -- Tao, Yuyong -- Cheung, Lily S -- Fan, Chao -- Chen, Li-Qing -- Xu, Sophia -- Perry, Kay -- Frommer, Wolf B -- Feng, Liang -- P41 GM103403/GM/NIGMS NIH HHS/ -- England -- Nature. 2014 Nov 20;515(7527):448-52. doi: 10.1038/nature13670. Epub 2014 Sep 3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Department of Molecular and Cellular Physiology, 279 Campus Drive, Stanford University School of Medicine, Stanford, California 94305, USA [2]. ; 1] Department of Plant Biology, Carnegie Institution for Science, 260 Panama Street, Stanford, California 94305, USA [2]. ; Department of Molecular and Cellular Physiology, 279 Campus Drive, Stanford University School of Medicine, Stanford, California 94305, USA. ; Department of Plant Biology, Carnegie Institution for Science, 260 Panama Street, Stanford, California 94305, USA. ; Department of Biology, Stanford University, Stanford, California 94305, USA. ; NE-CAT and Department of Chemistry and Chemical Biology, Cornell University, Building 436E, Argonne National Laboratory, 9700 South Cass Avenue, Argonne, Illinois 60439, USA. ; 1] Department of Plant Biology, Carnegie Institution for Science, 260 Panama Street, Stanford, California 94305, USA [2] Department of Biology, Stanford University, Stanford, California 94305, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25186729" target="_blank"〉PubMed〈/a〉
    Keywords: Arabidopsis/chemistry ; Bacterial Proteins/*chemistry/metabolism ; Crystallography, X-Ray ; Evolution, Molecular ; Glucose/metabolism ; Leptospira/*chemistry/genetics ; Models, Molecular ; Monosaccharide Transport Proteins/*chemistry/genetics/metabolism ; Movement ; Protein Conformation ; Protein Multimerization ; Structure-Activity Relationship ; Vibrio/*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
  • 51
    facet.materialart.
    Unknown
    Stereospecific targeting of MTH1 by (S)-crizotinib as an anticancer strategy (2014)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2014-04-04
    Description: Activated RAS GTPase signalling is a critical driver of oncogenic transformation and malignant disease. Cellular models of RAS-dependent cancers have been used to identify experimental small molecules, such as SCH51344, but their molecular mechanism of action remains generally unknown. Here, using a chemical proteomic approach, we identify the target of SCH51344 as the human mutT homologue MTH1 (also known as NUDT1), a nucleotide pool sanitizing enzyme. Loss-of-function of MTH1 impaired growth of KRAS tumour cells, whereas MTH1 overexpression mitigated sensitivity towards SCH51344. Searching for more drug-like inhibitors, we identified the kinase inhibitor crizotinib as a nanomolar suppressor of MTH1 activity. Surprisingly, the clinically used (R)-enantiomer of the drug was inactive, whereas the (S)-enantiomer selectively inhibited MTH1 catalytic activity. Enzymatic assays, chemical proteomic profiling, kinome-wide activity surveys and MTH1 co-crystal structures of both enantiomers provide a rationale for this remarkable stereospecificity. Disruption of nucleotide pool homeostasis via MTH1 inhibition by (S)-crizotinib induced an increase in DNA single-strand breaks, activated DNA repair in human colon carcinoma cells, and effectively suppressed tumour growth in animal models. Our results propose (S)-crizotinib as an attractive chemical entity for further pre-clinical evaluation, and small-molecule inhibitors of MTH1 in general as a promising novel class of anticancer agents.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4150021/" 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/PMC4150021/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Huber, Kilian V M -- Salah, Eidarus -- Radic, Branka -- Gridling, Manuela -- Elkins, Jonathan M -- Stukalov, Alexey -- Jemth, Ann-Sofie -- Gokturk, Camilla -- Sanjiv, Kumar -- Stromberg, Kia -- Pham, Therese -- Berglund, Ulrika Warpman -- Colinge, Jacques -- Bennett, Keiryn L -- Loizou, Joanna I -- Helleday, Thomas -- Knapp, Stefan -- Superti-Furga, Giulio -- 092809/Wellcome Trust/United Kingdom -- 092809/Z/10/Z/Wellcome Trust/United Kingdom -- F 4711/Austrian Science Fund FWF/Austria -- Canadian Institutes of Health Research/Canada -- England -- Nature. 2014 Apr 10;508(7495):222-7. doi: 10.1038/nature13194. Epub 2014 Apr 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 1090 Vienna, Austria. ; Nuffield Department of Clinical Medicine, Structural Genomics Consortium, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford OX3 7DQ, UK. ; Science for Life Laboratory, Division of Translational Medicine and Chemical Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, 17121 Stockholm, Sweden.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24695225" target="_blank"〉PubMed〈/a〉
    Keywords: Aminoquinolines/pharmacology ; Animals ; Antineoplastic Agents/chemistry/*pharmacology ; Colonic Neoplasms/drug therapy/genetics/pathology ; Crystallization ; DNA Breaks, Single-Stranded/drug effects ; DNA Repair ; DNA Repair Enzymes/*antagonists & inhibitors/biosynthesis/chemistry/*metabolism ; Disease Models, Animal ; Female ; Homeostasis/drug effects ; Humans ; Mice ; Mice, SCID ; Models, Molecular ; Nucleotides/metabolism ; Phosphoric Monoester Hydrolases/*antagonists & ; inhibitors/biosynthesis/chemistry/*metabolism ; Protein Conformation ; Protein Kinase Inhibitors/chemistry/*pharmacology ; Proteomics ; Proto-Oncogene Proteins/genetics ; Pyrazoles/chemistry/*pharmacology ; Pyridines/chemistry/*pharmacology ; Substrate Specificity ; Xenograft Model Antitumor Assays ; ras Proteins/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
  • 52
    facet.materialart.
    Unknown
    Agonist-bound structure of the human P2Y12 receptor (2014)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2014-05-03
    Description: The P2Y12 receptor (P2Y12R), one of eight members of the P2YR family expressed in humans, is one of the most prominent clinical drug targets for inhibition of platelet aggregation. Although mutagenesis and modelling studies of the P2Y12R provided useful insights into ligand binding, the agonist and antagonist recognition and function at the P2Y12R remain poorly understood at the molecular level. Here we report the structures of the human P2Y12R in complex with the full agonist 2-methylthio-adenosine-5'-diphosphate (2MeSADP, a close analogue of endogenous agonist ADP) at 2.5 A resolution, and the corresponding ATP derivative 2-methylthio-adenosine-5'-triphosphate (2MeSATP) at 3.1 A resolution. These structures, together with the structure of the P2Y12R with antagonist ethyl 6-(4-((benzylsulfonyl)carbamoyl)piperidin-1-yl)-5-cyano-2-methylnicotinate (AZD1283), reveal striking conformational changes between nucleotide and non-nucleotide ligand complexes in the extracellular regions. Further analysis of these changes provides insight into a distinct ligand binding landscape in the delta-group of class A G-protein-coupled receptors (GPCRs). Agonist and non-nucleotide antagonist adopt different orientations in the P2Y12R, with only partially overlapped binding pockets. The agonist-bound P2Y12R structure answers long-standing questions surrounding P2Y12R-agonist recognition, and reveals interactions with several residues that had not been reported to be involved in agonist binding. As a first example, to our knowledge, of a GPCR in which agonist access to the binding pocket requires large-scale rearrangements in the highly malleable extracellular region, the structural and docking studies will therefore provide invaluable insight into the pharmacology and mechanisms of action of agonists and different classes of antagonists for the P2Y12R and potentially for other closely related P2YRs.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4128917/" 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/PMC4128917/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhang, Jin -- Zhang, Kaihua -- Gao, Zhan-Guo -- Paoletta, Silvia -- Zhang, Dandan -- Han, Gye Won -- Li, Tingting -- Ma, Limin -- Zhang, Wenru -- Muller, Christa E -- Yang, Huaiyu -- Jiang, Hualiang -- Cherezov, Vadim -- Katritch, Vsevolod -- Jacobson, Kenneth A -- Stevens, Raymond C -- Wu, Beili -- Zhao, Qiang -- R01 AI100604/AI/NIAID NIH HHS/ -- R01AI100604/AI/NIAID NIH HHS/ -- U54 GM094618/GM/NIGMS NIH HHS/ -- U54GM094618/GM/NIGMS NIH HHS/ -- Intramural NIH HHS/ -- England -- Nature. 2014 May 1;509(7498):119-22. doi: 10.1038/nature13288.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Pudong, Shanghai 201203, China [2]. ; Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. ; CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Pudong, Shanghai 201203, China. ; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA. ; PharmaCenter Bonn, University of Bonn, Pharmaceutical Chemistry I, An der Immenburg 4, D-53121 Bonn, Germany. ; Drug Discovery and Design Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Pudong, Shanghai 201203, China. ; 1] Department of Integrative Structural and Computational Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA [2] iHuman Institute, ShanghaiTech University, 99 Haike Road, Pudong, Shanghai 201203, China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24784220" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Diphosphate/*analogs & derivatives/chemistry/metabolism ; Adenosine Triphosphate/*analogs & derivatives/chemistry/metabolism ; Binding Sites ; Crystallography, X-Ray ; Humans ; Ligands ; Models, Molecular ; Niacin/analogs & derivatives/chemistry/metabolism ; Protein Conformation ; Purinergic P2Y Receptor Agonists/*chemistry/metabolism ; Purinergic P2Y Receptor Antagonists/chemistry/metabolism ; Receptors, Purinergic P2Y12/*chemistry/metabolism ; Substrate Specificity ; Sulfonamides/chemistry/metabolism ; Thionucleotides/*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
  • 53
    facet.materialart.
    Unknown
    ANP32E is a histone chaperone that removes H2A.Z from chromatin (2014)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2014-01-28
    Description: H2A.Z is an essential histone variant implicated in the regulation of key nuclear events. However, the metazoan chaperones responsible for H2A.Z deposition and its removal from chromatin remain unknown. Here we report the identification and characterization of the human protein ANP32E as a specific H2A.Z chaperone. We show that ANP32E is a member of the presumed H2A.Z histone-exchange complex p400/TIP60. ANP32E interacts with a short region of the docking domain of H2A.Z through a new motif termed H2A.Z interacting domain (ZID). The 1.48 A resolution crystal structure of the complex formed between the ANP32E-ZID and the H2A.Z/H2B dimer and biochemical data support an underlying molecular mechanism for H2A.Z/H2B eviction from the nucleosome and its stabilization by ANP32E through a specific extension of the H2A.Z carboxy-terminal alpha-helix. Finally, analysis of H2A.Z localization in ANP32E(-/-) cells by chromatin immunoprecipitation followed by sequencing shows genome-wide enrichment, redistribution and accumulation of H2A.Z at specific chromatin control regions, in particular at enhancers and insulators.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Obri, Arnaud -- Ouararhni, Khalid -- Papin, Christophe -- Diebold, Marie-Laure -- Padmanabhan, Kiran -- Marek, Martin -- Stoll, Isabelle -- Roy, Ludovic -- Reilly, Patrick T -- Mak, Tak W -- Dimitrov, Stefan -- Romier, Christophe -- Hamiche, Ali -- England -- Nature. 2014 Jan 30;505(7485):648-53. doi: 10.1038/nature12922. Epub 2014 Jan 22.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Departement de Genomique Fonctionnelle et Cancer, Institut de Genetique et Biologie Moleculaire et Cellulaire (IGBMC), Universite de Strasbourg, CNRS, INSERM, 1 rue Laurent Fries, B.P. 10142, 67404 Illkirch Cedex, France [2]. ; Departement de Biologie Structurale Integrative, Institut de Genetique et Biologie Moleculaire et Cellulaire (IGBMC), Universite de Strasbourg, CNRS, INSERM, 1 rue Laurent Fries, B.P. 10142, 67404 Illkirch Cedex, France. ; Equipe labelisee Ligue contre le Cancer, INSERM/Universite Joseph Fourier , Institut Albert Bonniot, U823, Site Sante-BP 170, 38042 Grenoble Cedex 9, France. ; Departement de Genomique Fonctionnelle et Cancer, Institut de Genetique et Biologie Moleculaire et Cellulaire (IGBMC), Universite de Strasbourg, CNRS, INSERM, 1 rue Laurent Fries, B.P. 10142, 67404 Illkirch Cedex, France. ; Laboratory of Inflammation Biology, Division of Cellular and Molecular Research, National Cancer Centre, Singapore, Singapore. ; 1] Laboratory of Inflammation Biology, Division of Cellular and Molecular Research, National Cancer Centre, Singapore, Singapore [2] The Campbell Family Institute for Breast Cancer Research, University Health Network, Toronto, Ontario, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24463511" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Cell Line ; Cell Nucleus/chemistry/metabolism ; Chromatin/*chemistry/genetics/*metabolism ; Chromatin Immunoprecipitation ; Crystallography, X-Ray ; DNA/genetics/metabolism ; Genome, Human/genetics ; Histones/chemistry/isolation & purification/*metabolism ; Humans ; Models, Molecular ; Molecular Chaperones/chemistry/*metabolism ; Molecular Sequence Data ; Nuclear Proteins/chemistry/*metabolism ; Nucleosomes/chemistry/metabolism ; Phosphoproteins/chemistry/*metabolism ; Protein Binding ; Protein Conformation ; 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
    Structure of the human P2Y12 receptor in complex with an antithrombotic drug (2014)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2014-03-29
    Description: P2Y receptors (P2YRs), a family of purinergic G-protein-coupled receptors (GPCRs), are activated by extracellular nucleotides. There are a total of eight distinct functional P2YRs expressed in human, which are subdivided into P2Y1-like receptors and P2Y12-like receptors. Their ligands are generally charged molecules with relatively low bioavailability and stability in vivo, which limits our understanding of this receptor family. P2Y12R regulates platelet activation and thrombus formation, and several antithrombotic drugs targeting P2Y12R--including the prodrugs clopidogrel (Plavix) and prasugrel (Effient) that are metabolized and bind covalently, and the nucleoside analogue ticagrelor (Brilinta) that acts directly on the receptor--have been approved for the prevention of stroke and myocardial infarction. However, limitations of these drugs (for example, a very long half-life of clopidogrel action and a characteristic adverse effect profile of ticagrelor) suggest that there is an unfulfilled medical need for developing a new generation of P2Y12R inhibitors. Here we report the 2.6 A resolution crystal structure of human P2Y12R in complex with a non-nucleotide reversible antagonist, AZD1283. The structure reveals a distinct straight conformation of helix V, which sets P2Y12R apart from all other known class A GPCR structures. With AZD1283 bound, the highly conserved disulphide bridge in GPCRs between helix III and extracellular loop 2 is not observed and appears to be dynamic. Along with the details of the AZD1283-binding site, analysis of the extracellular interface reveals an adjacent ligand-binding region and suggests that both pockets could be required for dinucleotide binding. The structure provides essential insights for the development of improved P2Y12R ligands and allosteric modulators as drug candidates.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4174307/" 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/PMC4174307/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhang, Kaihua -- Zhang, Jin -- Gao, Zhan-Guo -- Zhang, Dandan -- Zhu, Lan -- Han, Gye Won -- Moss, Steven M -- Paoletta, Silvia -- Kiselev, Evgeny -- Lu, Weizhen -- Fenalti, Gustavo -- Zhang, Wenru -- Muller, Christa E -- Yang, Huaiyu -- Jiang, Hualiang -- Cherezov, Vadim -- Katritch, Vsevolod -- Jacobson, Kenneth A -- Stevens, Raymond C -- Wu, Beili -- Zhao, Qiang -- R01 AI100604/AI/NIAID NIH HHS/ -- U54 GM094618/GM/NIGMS NIH HHS/ -- Z99 DK999999/Intramural NIH HHS/ -- ZIA DK031116-26/Intramural NIH HHS/ -- ZIA DK031126-07/Intramural NIH HHS/ -- England -- Nature. 2014 May 1;509(7498):115-8. doi: 10.1038/nature13083. Epub 2014 Mar 23.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Pudong, Shanghai 201203, China [2]. ; Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. ; CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Pudong, Shanghai 201203, China. ; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA. ; PharmaCenter Bonn, Pharmaceutical Institute, Pharmaceutical Chemistry I, An der Immenburg 4, D-53121 Bonn, Germany. ; Drug Discovery and Design Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Pudong, Shanghai 201203, China. ; 1] Department of Integrative Structural and Computational Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA [2] iHuman Institute, ShanghaiTech University, 99 Haike Road, Pudong, Shanghai 201203, China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24670650" target="_blank"〉PubMed〈/a〉
    Keywords: Binding Sites ; Crystallography, X-Ray ; Disulfides/metabolism ; Fibrinolytic Agents/*chemistry ; Humans ; Ligands ; Models, Molecular ; Molecular Docking Simulation ; Niacin/*analogs & derivatives/chemistry/metabolism ; Protein Conformation ; Purinergic P2Y Receptor Antagonists/chemistry/metabolism ; Receptors, Purinergic P2Y12/*chemistry/metabolism ; Sulfonamides/*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
  • 55
    facet.materialart.
    Unknown
    Proof of principle for epitope-focused vaccine design (2014)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2014-02-07
    Description: Vaccines prevent infectious disease largely by inducing protective neutralizing antibodies against vulnerable epitopes. Several major pathogens have resisted traditional vaccine development, although vulnerable epitopes targeted by neutralizing antibodies have been identified for several such cases. Hence, new vaccine design methods to induce epitope-specific neutralizing antibodies are needed. Here we show, with a neutralization epitope from respiratory syncytial virus, that computational protein design can generate small, thermally and conformationally stable protein scaffolds that accurately mimic the viral epitope structure and induce potent neutralizing antibodies. These scaffolds represent promising leads for the research and development of a human respiratory syncytial virus vaccine needed to protect infants, young children and the elderly. More generally, the results provide proof of principle for epitope-focused and scaffold-based vaccine design, and encourage the evaluation and further development of these strategies for a variety of other vaccine targets, including antigenically highly variable pathogens such as human immunodeficiency virus and influenza.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4260937/" 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/PMC4260937/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Correia, Bruno E -- Bates, John T -- Loomis, Rebecca J -- Baneyx, Gretchen -- Carrico, Chris -- Jardine, Joseph G -- Rupert, Peter -- Correnti, Colin -- Kalyuzhniy, Oleksandr -- Vittal, Vinayak -- Connell, Mary J -- Stevens, Eric -- Schroeter, Alexandria -- Chen, Man -- Macpherson, Skye -- Serra, Andreia M -- Adachi, Yumiko -- Holmes, Margaret A -- Li, Yuxing -- Klevit, Rachel E -- Graham, Barney S -- Wyatt, Richard T -- Baker, David -- Strong, Roland K -- Crowe, James E Jr -- Johnson, Philip R -- Schief, William R -- 1R01AI102766-01A1/AI/NIAID NIH HHS/ -- 1UM1AI100663/AI/NIAID NIH HHS/ -- 2T32GM007270/GM/NIGMS NIH HHS/ -- 5R21AI088554/AI/NIAID NIH HHS/ -- P01 AI094419/AI/NIAID NIH HHS/ -- P01AI094419/AI/NIAID NIH HHS/ -- P30 AI036214/AI/NIAID NIH HHS/ -- P30 AI045008/AI/NIAID NIH HHS/ -- P30AI36214/AI/NIAID NIH HHS/ -- R01 AI102766/AI/NIAID NIH HHS/ -- R21 AI088554/AI/NIAID NIH HHS/ -- T32 CA080416/CA/NCI NIH HHS/ -- T32 GM007270/GM/NIGMS NIH HHS/ -- T32CA080416/CA/NCI NIH HHS/ -- U54 AI 005714/AI/NIAID NIH HHS/ -- U54 AI057141/AI/NIAID NIH HHS/ -- UM1 AI100663/AI/NIAID NIH HHS/ -- Intramural NIH HHS/ -- England -- Nature. 2014 Mar 13;507(7491):201-6. doi: 10.1038/nature12966. Epub 2014 Feb 5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Department of Biochemistry, University of Washington, Seattle, Washington 98195, USA [2] PhD Program in Computational Biology, Instituto Gulbenkian Ciencia and Instituto de Tecnologia Quimica e Biologica, Universidade Nova de Lisboa, Oeiras 2780-157, Portugal [3] Department of Chemical Physiology, The Scripps Research Institute, La Jolla, California 92037, USA. ; The Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA. ; The Children's Hospital of Philadelphia Research Institute, Philadelphia, Pennsylvania 19104, USA. ; Department of Biochemistry, University of Washington, Seattle, Washington 98195, USA. ; Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109-1024, USA. ; 1] Department of Biochemistry, University of Washington, Seattle, Washington 98195, USA [2] Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, California 92037, USA [3] IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, California 92037, USA [4] Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, California 92037, USA. ; 1] Department of Biochemistry, University of Washington, Seattle, Washington 98195, USA [2] IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, California 92037, USA [3] Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, California 92037, USA. ; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. ; 1] Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109-1024, USA [2]. ; 1] Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, California 92037, USA [2] IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, California 92037, USA [3] Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, California 92037, USA. ; 1] The Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA [2] Department of Pathology, Microbiology and Immunology, Vanderbilt Medical Center, Nashville, Tennessee 37232, USA [3] Department of Pediatrics, Vanderbilt Medical Center, Nashville, Tennessee 37232, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24499818" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Motifs ; Animals ; Antibodies, Monoclonal/analysis/immunology ; Antibodies, Neutralizing/analysis/immunology ; Antibodies, Viral/analysis/immunology ; Antigens, Viral/chemistry/immunology ; Crystallography, X-Ray ; *Drug Design ; Enzyme-Linked Immunosorbent Assay ; Epitopes/*chemistry/*immunology ; Macaca mulatta/immunology ; Male ; Mice ; Mice, Inbred BALB C ; Models, Molecular ; Neutralization Tests ; Protein Conformation ; *Protein Stability ; Respiratory Syncytial Virus Vaccines/*chemistry/*immunology ; Respiratory Syncytial Viruses/chemistry/immunology
    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
    ZMYND11 links histone H3.3K36me3 to transcription elongation and tumour suppression (2014)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2014-03-05
    Description: Recognition of modified histones by 'reader' proteins plays a critical role in the regulation of chromatin. H3K36 trimethylation (H3K36me3) is deposited onto the nucleosomes in the transcribed regions after RNA polymerase II elongation. In yeast, this mark in turn recruits epigenetic regulators to reset the chromatin to a relatively repressive state, thus suppressing cryptic transcription. However, much less is known about the role of H3K36me3 in transcription regulation in mammals. This is further complicated by the transcription-coupled incorporation of the histone variant H3.3 in gene bodies. Here we show that the candidate tumour suppressor ZMYND11 specifically recognizes H3K36me3 on H3.3 (H3.3K36me3) and regulates RNA polymerase II elongation. Structural studies show that in addition to the trimethyl-lysine binding by an aromatic cage within the PWWP domain, the H3.3-dependent recognition is mediated by the encapsulation of the H3.3-specific 'Ser 31' residue in a composite pocket formed by the tandem bromo-PWWP domains of ZMYND11. Chromatin immunoprecipitation followed by sequencing shows a genome-wide co-localization of ZMYND11 with H3K36me3 and H3.3 in gene bodies, and its occupancy requires the pre-deposition of H3.3K36me3. Although ZMYND11 is associated with highly expressed genes, it functions as an unconventional transcription co-repressor by modulating RNA polymerase II at the elongation stage. ZMYND11 is critical for the repression of a transcriptional program that is essential for tumour cell growth; low expression levels of ZMYND11 in breast cancer patients correlate with worse prognosis. Consistently, overexpression of ZMYND11 suppresses cancer cell growth in vitro and tumour formation in mice. Together, this study identifies ZMYND11 as an H3.3-specific reader of H3K36me3 that links the histone-variant-mediated transcription elongation control to tumour suppression.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4142212/" 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/PMC4142212/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wen, Hong -- Li, Yuanyuan -- Xi, Yuanxin -- Jiang, Shiming -- Stratton, Sabrina -- Peng, Danni -- Tanaka, Kaori -- Ren, Yongfeng -- Xia, Zheng -- Wu, Jun -- Li, Bing -- Barton, Michelle C -- Li, Wei -- Li, Haitao -- Shi, Xiaobing -- CA016672/CA/NCI NIH HHS/ -- P30 CA016672/CA/NCI NIH HHS/ -- R01 GM090077/GM/NIGMS NIH HHS/ -- R01 HG007538/HG/NHGRI NIH HHS/ -- R01GM090077/GM/NIGMS NIH HHS/ -- R01HG007538/HG/NHGRI NIH HHS/ -- England -- Nature. 2014 Apr 10;508(7495):263-8. doi: 10.1038/nature13045. Epub 2014 Mar 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Department of Biochemistry and Molecular Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA [2] Center for Cancer Epigenetics, Center for Genetics and Genomics, and Center for Stem Cell and Developmental Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA [3]. ; 1] MOE Key Laboratory of Protein Sciences, Center for Structural Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China [2] Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing 100084, China [3]. ; 1] Dan L. Duncan Cancer Center, Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA [2]. ; Department of Biochemistry and Molecular Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA. ; 1] MOE Key Laboratory of Protein Sciences, Center for Structural Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China [2] Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing 100084, China. ; Dan L. Duncan Cancer Center, Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA. ; Department of Molecular Biology, The University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA. ; 1] Department of Biochemistry and Molecular Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA [2] Center for Cancer Epigenetics, Center for Genetics and Genomics, and Center for Stem Cell and Developmental Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA [3] Genes and Development Graduate Program, The University of Texas Graduate School of Biomedical Sciences, Houston, Teaxs 77030, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24590075" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Breast Neoplasms/*genetics/metabolism/*pathology ; Carrier Proteins/chemistry/*metabolism ; Chromatin/genetics/metabolism ; Co-Repressor Proteins/chemistry/metabolism ; Crystallography, X-Ray ; Disease-Free Survival ; Female ; Gene Expression Regulation, Neoplastic/genetics ; Histones/chemistry/*metabolism ; Humans ; Lysine/*metabolism ; Methylation ; Mice ; Mice, Nude ; Models, Molecular ; Molecular Sequence Data ; Oncogenes/genetics ; Prognosis ; Protein Binding ; Protein Conformation ; Protein Structure, Tertiary ; RNA Polymerase II/*metabolism ; Substrate Specificity ; *Transcription Elongation, 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
  • 57
    facet.materialart.
    Unknown
    Neurodegeneration: Alzheimer's disease under strain (2014)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2014-08-08
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Aguzzi, Adriano -- England -- Nature. 2014 Aug 7;512(7512):32-4. doi: 10.1038/512032a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Neuropathology, University Hospital Zurich, Zurich CH-8091,Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25100477" target="_blank"〉PubMed〈/a〉
    Keywords: Alzheimer Disease/*classification/epidemiology/*metabolism/therapy ; Amyloid beta-Peptides/*chemistry/*classification/genetics/metabolism ; Animals ; Antibody Specificity ; Arctic Regions ; Cattle ; Humans ; Mice ; *Models, Biological ; Prion Diseases/classification/metabolism/pathology/transmission ; 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
  • 58
    facet.materialart.
    Unknown
    Historical contingency and its biophysical basis in glucocorticoid receptor evolution (2014)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2014-06-17
    Description: Understanding how chance historical events shape evolutionary processes is a central goal of evolutionary biology. Direct insights into the extent and causes of evolutionary contingency have been limited to experimental systems, because it is difficult to know what happened in the deep past and to characterize other paths that evolution could have followed. Here we combine ancestral protein reconstruction, directed evolution and biophysical analysis to explore alternative 'might-have-been' trajectories during the ancient evolution of a novel protein function. We previously found that the evolution of cortisol specificity in the ancestral glucocorticoid receptor (GR) was contingent on permissive substitutions, which had no apparent effect on receptor function but were necessary for GR to tolerate the large-effect mutations that caused the shift in specificity. Here we show that alternative mutations that could have permitted the historical function-switching substitutions are extremely rare in the ensemble of genotypes accessible to the ancestral GR. In a library of thousands of variants of the ancestral protein, we recovered historical permissive substitutions but no alternative permissive genotypes. Using biophysical analysis, we found that permissive mutations must satisfy at least three physical requirements--they must stabilize specific local elements of the protein structure, maintain the correct energetic balance between functional conformations, and be compatible with the ancestral and derived structures--thus revealing why permissive mutations are rare. These findings demonstrate that GR evolution depended strongly on improbable, non-deterministic events, and this contingency arose from intrinsic biophysical properties of the protein.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4447330/" 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/PMC4447330/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Harms, Michael J -- Thornton, Joseph W -- F32-GM090650/GM/NIGMS NIH HHS/ -- R01 GM081592/GM/NIGMS NIH HHS/ -- R01 GM104397/GM/NIGMS NIH HHS/ -- R01-GM081592/GM/NIGMS NIH HHS/ -- R01-GM104397/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2014 Aug 14;512(7513):203-7. doi: 10.1038/nature13410. Epub 2014 Jun 15.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Institute of Molecular Biology and Department of Chemistry &Biochemistry, University of Oregon, Eugene, Oregon 97403, USA [2] Departments of Human Genetics and Ecology &Evolution, University of Chicago, Chicago, Illinois 60637, USA. ; 1] Departments of Human Genetics and Ecology &Evolution, University of Chicago, Chicago, Illinois 60637, USA [2] Institute of Ecology and Evolution, University of Oregon, Eugene, Oregon 97403, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24930765" target="_blank"〉PubMed〈/a〉
    Keywords: Biophysics ; *Evolution, Molecular ; Genotype ; Mutation/genetics ; Protein Conformation ; Protein Stability ; Receptors, Glucocorticoid/*chemistry/*genetics ; Saccharomyces cerevisiae ; Substrate Specificity ; Two-Hybrid System Techniques
    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
    CEACAM1 regulates TIM-3-mediated tolerance and exhaustion (2014)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2014-11-05
    Description: T-cell immunoglobulin domain and mucin domain-3 (TIM-3, also known as HAVCR2) is an activation-induced inhibitory molecule involved in tolerance and shown to induce T-cell exhaustion in chronic viral infection and cancers. Under some conditions, TIM-3 expression has also been shown to be stimulatory. Considering that TIM-3, like cytotoxic T lymphocyte antigen 4 (CTLA-4) and programmed death 1 (PD-1), is being targeted for cancer immunotherapy, it is important to identify the circumstances under which TIM-3 can inhibit and activate T-cell responses. Here we show that TIM-3 is co-expressed and forms a heterodimer with carcinoembryonic antigen cell adhesion molecule 1 (CEACAM1), another well-known molecule expressed on activated T cells and involved in T-cell inhibition. Biochemical, biophysical and X-ray crystallography studies show that the membrane-distal immunoglobulin-variable (IgV)-like amino-terminal domain of each is crucial to these interactions. The presence of CEACAM1 endows TIM-3 with inhibitory function. CEACAM1 facilitates the maturation and cell surface expression of TIM-3 by forming a heterodimeric interaction in cis through the highly related membrane-distal N-terminal domains of each molecule. CEACAM1 and TIM-3 also bind in trans through their N-terminal domains. Both cis and trans interactions between CEACAM1 and TIM-3 determine the tolerance-inducing function of TIM-3. In a mouse adoptive transfer colitis model, CEACAM1-deficient T cells are hyper-inflammatory with reduced cell surface expression of TIM-3 and regulatory cytokines, and this is restored by T-cell-specific CEACAM1 expression. During chronic viral infection and in a tumour environment, CEACAM1 and TIM-3 mark exhausted T cells. Co-blockade of CEACAM1 and TIM-3 leads to enhancement of anti-tumour immune responses with improved elimination of tumours in mouse colorectal cancer models. Thus, CEACAM1 serves as a heterophilic ligand for TIM-3 that is required for its ability to mediate T-cell inhibition, and this interaction has a crucial role in regulating autoimmunity and anti-tumour immunity.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4297519/" 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/PMC4297519/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Huang, Yu-Hwa -- Zhu, Chen -- Kondo, Yasuyuki -- Anderson, Ana C -- Gandhi, Amit -- Russell, Andrew -- Dougan, Stephanie K -- Petersen, Britt-Sabina -- Melum, Espen -- Pertel, Thomas -- Clayton, Kiera L -- Raab, Monika -- Chen, Qiang -- Beauchemin, Nicole -- Yazaki, Paul J -- Pyzik, Michal -- Ostrowski, Mario A -- Glickman, Jonathan N -- Rudd, Christopher E -- Ploegh, Hidde L -- Franke, Andre -- Petsko, Gregory A -- Kuchroo, Vijay K -- Blumberg, Richard S -- AI039671/AI/NIAID NIH HHS/ -- AI056299/AI/NIAID NIH HHS/ -- AI073748/AI/NIAID NIH HHS/ -- DK0034854/DK/NIDDK NIH HHS/ -- DK044319/DK/NIDDK NIH HHS/ -- DK051362/DK/NIDDK NIH HHS/ -- DK053056/DK/NIDDK NIH HHS/ -- DK088199/DK/NIDDK NIH HHS/ -- GM32415/GM/NIGMS NIH HHS/ -- MOP-93787/Canadian Institutes of Health Research/Canada -- NS045937/NS/NINDS NIH HHS/ -- P01 AI039671/AI/NIAID NIH HHS/ -- P01 AI056299/AI/NIAID NIH HHS/ -- P01 AI073748/AI/NIAID NIH HHS/ -- P30 DK034854/DK/NIDDK NIH HHS/ -- P41 GM111244/GM/NIGMS NIH HHS/ -- R01 DK051362/DK/NIDDK NIH HHS/ -- R01 GM026788/GM/NIGMS NIH HHS/ -- R01 NS045937/NS/NINDS NIH HHS/ -- T32 GM007122/GM/NIGMS NIH HHS/ -- UL1 TR001102/TR/NCATS NIH HHS/ -- England -- Nature. 2015 Jan 15;517(7534):386-90. doi: 10.1038/nature13848. Epub 2014 Oct 26.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Gastroenterology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, Massachusetts 02115, USA. ; Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Harvard Institutes of Medicine, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA. ; Rosenstiel Basic Medical Sciences Research Center, Brandeis University, 415 South Street, Waltham, Massachusetts 02454, USA. ; Whitehead Institute, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA. ; Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel 24105, Germany. ; 1] Division of Gastroenterology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, Massachusetts 02115, USA [2] Norwegian PSC Research Center, Division of Cancer Medicine, Surgery and Transplantation, Oslo University Hospital, Oslo 0424, Norway. ; Department of Immunology, University of Toronto, Toronto, Ontario M5S1A8, Canada. ; Cell Signalling Section, Department of Pathology, University of Cambridge, Cambridge CB2 1QP, UK. ; State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China. ; Goodman Cancer Research Centre, McGill University, Montreal H3G 1Y6, Canada. ; Beckman Institute, City of Hope, Duarte, California 91010, USA. ; 1] Department of Immunology, University of Toronto, Toronto, Ontario M5S1A8, Canada [2] Keenan Research Centre of St. Michael's Hospital, Toronto, Ontario M5S1A8, Canada. ; GI Pathology, Miraca Life Sciences, Newton, Massachusetts 02464, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25363763" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens, CD/chemistry/immunology/*metabolism ; Autoimmunity/immunology ; Cell Adhesion Molecules/chemistry/immunology/*metabolism ; Cell Line ; Colorectal Neoplasms/immunology ; Disease Models, Animal ; Female ; Humans ; Immune Tolerance/*immunology ; Inflammation/immunology/pathology ; Ligands ; Male ; Membrane Proteins/chemistry/immunology/*metabolism ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Models, Molecular ; Mucous Membrane/immunology/pathology ; Protein Conformation ; Protein Multimerization ; Receptors, Virus/chemistry/immunology/*metabolism ; T-Lymphocytes/*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
  • 60
    facet.materialart.
    Unknown
    Structural and mechanistic insights into the bacterial amyloid secretion channel CsgG (2014)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2014-09-16
    Description: Curli are functional amyloid fibres that constitute the major protein component of the extracellular matrix in pellicle biofilms formed by Bacteroidetes and Proteobacteria (predominantly of the alpha and gamma classes). They provide a fitness advantage in pathogenic strains and induce a strong pro-inflammatory response during bacteraemia. Curli formation requires a dedicated protein secretion machinery comprising the outer membrane lipoprotein CsgG and two soluble accessory proteins, CsgE and CsgF. Here we report the X-ray structure of Escherichia coli CsgG in a non-lipidated, soluble form as well as in its native membrane-extracted conformation. CsgG forms an oligomeric transport complex composed of nine anticodon-binding-domain-like units that give rise to a 36-stranded beta-barrel that traverses the bilayer and is connected to a cage-like vestibule in the periplasm. The transmembrane and periplasmic domains are separated by a 0.9-nm channel constriction composed of three stacked concentric phenylalanine, asparagine and tyrosine rings that may guide the extended polypeptide substrate through the secretion pore. The specificity factor CsgE forms a nonameric adaptor that binds and closes off the periplasmic face of the secretion channel, creating a 24,000 A(3) pre-constriction chamber. Our structural, functional and electrophysiological analyses imply that CsgG is an ungated, non-selective protein secretion channel that is expected to employ a diffusion-based, entropy-driven transport mechanism.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4268158/" 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/PMC4268158/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Goyal, Parveen -- Krasteva, Petya V -- Van Gerven, Nani -- Gubellini, Francesca -- Van den Broeck, Imke -- Troupiotis-Tsailaki, Anastassia -- Jonckheere, Wim -- Pehau-Arnaudet, Gerard -- Pinkner, Jerome S -- Chapman, Matthew R -- Hultgren, Scott J -- Howorka, Stefan -- Fronzes, Remi -- Remaut, Han -- R01 A1073847/PHS HHS/ -- R01 AI048689/AI/NIAID NIH HHS/ -- R01 AI073847/AI/NIAID NIH HHS/ -- R01 AI099099/AI/NIAID NIH HHS/ -- R56 AI073847/AI/NIAID NIH HHS/ -- England -- Nature. 2014 Dec 11;516(7530):250-3. doi: 10.1038/nature13768. Epub 2014 Sep 14.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Structural and Molecular Microbiology, Structural Biology Research Center, VIB, Pleinlaan 2, 1050 Brussels, Belgium [2] Structural Biology Brussels, Vrije Universiteit Brussel, Pleinlaan 2, 1050 Brussels, Belgium. ; 1] Unite G5 Biologie structurale de la secretion bacterienne, Institut Pasteur, 25-28 rue du Docteur Roux, 75015 Paris, France [2] UMR 3528, CNRS, Institut Pasteur, 25-28 rue du Docteur Roux, 75015 Paris, France. ; Structure et Fonction des Membranes Biologiques (SFMB), Universite Libre de Bruxelles, 1050 Brussels, Belgium. ; UMR 3528, CNRS, Institut Pasteur, 25-28 rue du Docteur Roux, 75015 Paris, France. ; Department of Molecular Microbiology and Microbial Pathogenesis, Washington University in Saint Louis School of Medicine, St Louis, Missouri 63110-1010, USA. ; Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, Michigan 48109-1048, USA. ; Department of Chemistry, Institute for Structural and Molecular Biology, University College London, London WC1H 0AJ, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25219853" target="_blank"〉PubMed〈/a〉
    Keywords: Amyloid/*secretion ; Biofilms ; Cell Membrane ; Crystallography, X-Ray ; Diffusion ; Entropy ; Escherichia coli/*chemistry ; Escherichia coli Proteins/*chemistry/*metabolism ; Lipoproteins/*chemistry/*metabolism ; Membrane Transport Proteins/metabolism ; Models, Biological ; Models, Molecular ; Periplasm/metabolism ; Protein Conformation ; Protein Transport
    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
    Protein-guided RNA dynamics during early ribosome assembly (2014)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2014-02-14
    Description: The assembly of 30S ribosomes requires the precise addition of 20 proteins to the 16S ribosomal RNA. How early binding proteins change the ribosomal RNA structure so that later proteins may join the complex is poorly understood. Here we use single-molecule fluorescence resonance energy transfer (FRET) to observe real-time encounters between Escherichia coli ribosomal protein S4 and the 16S 5' domain RNA at an early stage of 30S assembly. Dynamic initial S4-RNA complexes pass through a stable non-native intermediate before converting to the native complex, showing that non-native structures can offer a low free-energy path to protein-RNA recognition. Three-colour FRET and molecular dynamics simulations reveal how S4 changes the frequency and direction of RNA helix motions, guiding a conformational switch that enforces the hierarchy of protein addition. These protein-guided dynamics offer an alternative explanation for induced fit in RNA-protein complexes.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3968076/" 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/PMC3968076/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kim, Hajin -- Abeysirigunawarden, Sanjaya C -- Chen, Ke -- Mayerle, Megan -- Ragunathan, Kaushik -- Luthey-Schulten, Zaida -- Ha, Taekjip -- Woodson, Sarah A -- R01 GM060819/GM/NIGMS NIH HHS/ -- R01 GM065367/GM/NIGMS NIH HHS/ -- R01 GM60819/GM/NIGMS NIH HHS/ -- R01 GM65367/GM/NIGMS NIH HHS/ -- T32 GM007231/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2014 Feb 20;506(7488):334-8. doi: 10.1038/nature13039. Epub 2014 Feb 12.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Department of Physics, Center for the Physics of Living Cells and Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA [2] Howard Hughes Medical Institute, Urbana, Illinois 61801, USA [3] [4] School of Nano-Bioscience and Chemical Engineering, Ulsan National Institute of Science and Technology, Ulsan 689-798, Republic of Korea (H.K.); Department of Biochemistry and Biophysics, University of California at San Francisco, 600 16th Street, San Francisco, California 94143-2200, USA (M.M.); Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, LHRRB-517, Boston, Massachusetts 02115-5730, USA (K.R.). ; 1] T. C. Jenkins Department of Biophysics, Johns Hopkins University, 3400 N. Charles Street, Baltimore, Maryland 21218, USA [2]. ; 1] Center for Biophysics and Computational Biology, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA [2] Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA. ; 1] CMDB Program, Johns Hopkins University, 3400 N. Charles Street, Baltimore, Maryland 21218, USA [2] School of Nano-Bioscience and Chemical Engineering, Ulsan National Institute of Science and Technology, Ulsan 689-798, Republic of Korea (H.K.); Department of Biochemistry and Biophysics, University of California at San Francisco, 600 16th Street, San Francisco, California 94143-2200, USA (M.M.); Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, LHRRB-517, Boston, Massachusetts 02115-5730, USA (K.R.). ; 1] Center for Biophysics and Computational Biology, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA [2] School of Nano-Bioscience and Chemical Engineering, Ulsan National Institute of Science and Technology, Ulsan 689-798, Republic of Korea (H.K.); Department of Biochemistry and Biophysics, University of California at San Francisco, 600 16th Street, San Francisco, California 94143-2200, USA (M.M.); Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, LHRRB-517, Boston, Massachusetts 02115-5730, USA (K.R.). ; 1] Department of Physics, Center for the Physics of Living Cells and Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA [2] Center for Biophysics and Computational Biology, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA [3] Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA. ; 1] Department of Physics, Center for the Physics of Living Cells and Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA [2] Howard Hughes Medical Institute, Urbana, Illinois 61801, USA [3] Center for Biophysics and Computational Biology, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA [4] Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA. ; 1] T. C. Jenkins Department of Biophysics, Johns Hopkins University, 3400 N. Charles Street, Baltimore, Maryland 21218, USA [2] CMDB Program, Johns Hopkins University, 3400 N. Charles Street, Baltimore, Maryland 21218, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24522531" target="_blank"〉PubMed〈/a〉
    Keywords: Escherichia coli/chemistry/genetics ; Fluorescence Resonance Energy Transfer ; Kinetics ; Models, Molecular ; *Molecular Dynamics Simulation ; Nucleic Acid Conformation ; Protein Binding ; Protein Conformation ; RNA, Ribosomal, 16S/*chemistry/*metabolism ; RNA-Binding Proteins/chemistry/metabolism ; Ribosomal Proteins/chemistry/*metabolism ; Ribosome Subunits, Small, Bacterial/*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
  • 62
    facet.materialart.
    Unknown
    Visualizing the kinetic power stroke that drives proton-coupled zinc(II) transport (2014)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2014-07-22
    Description: The proton gradient is a principal energy source for respiration-dependent active transport, but the structural mechanisms of proton-coupled transport processes are poorly understood. YiiP is a proton-coupled zinc transporter found in the cytoplasmic membrane of Escherichia coli. Its transport site receives protons from water molecules that gain access to its hydrophobic environment and transduces the energy of an inward proton gradient to drive Zn(II) efflux. This membrane protein is a well-characterized member of the family of cation diffusion facilitators that occurs at all phylogenetic levels. Here we show, using X-ray-mediated hydroxyl radical labelling of YiiP and mass spectrometry, that Zn(II) binding triggers a highly localized, all-or-nothing change of water accessibility to the transport site and an adjacent hydrophobic gate. Millisecond time-resolved dynamics reveal a concerted and reciprocal pattern of accessibility changes along a transmembrane helix, suggesting a rigid-body helical re-orientation linked to Zn(II) binding that triggers the closing of the hydrophobic gate. The gated water access to the transport site enables a stationary proton gradient to facilitate the conversion of zinc-binding energy to the kinetic power stroke of a vectorial zinc transport. The kinetic details provide energetic insights into a proton-coupled active-transport reaction.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4144069/" 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/PMC4144069/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gupta, Sayan -- Chai, Jin -- Cheng, Jie -- D'Mello, Rhijuta -- Chance, Mark R -- Fu, Dax -- P30 DK089502/DK/NIDDK NIH HHS/ -- P30-EB-09998/EB/NIBIB NIH HHS/ -- R01 GM065137/GM/NIGMS NIH HHS/ -- R01-EB-09688/EB/NIBIB NIH HHS/ -- R01GM065137/GM/NIGMS NIH HHS/ -- UL1 TR000439/TR/NCATS NIH HHS/ -- England -- Nature. 2014 Aug 7;512(7512):101-4. doi: 10.1038/nature13382. Epub 2014 Jun 22.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Center for Synchrotron Biosciences and Center for Proteomics and Bioinformatics, Case Western Reserve University, Cleveland, Ohio 44109, USA [2] Berkeley Center for Structural Biology, Physical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA. ; Biology Department, Brookhaven National Laboratory, Upton, New York 11973, USA. ; Department of Physiology, Johns Hopkins School of Medicine, Baltimore, Maryland 21205, USA. ; Center for Synchrotron Biosciences and Center for Proteomics and Bioinformatics, Case Western Reserve University, Cleveland, Ohio 44109, USA. ; 1] Biology Department, Brookhaven National Laboratory, Upton, New York 11973, USA [2] Department of Physiology, Johns Hopkins School of Medicine, Baltimore, Maryland 21205, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25043033" target="_blank"〉PubMed〈/a〉
    Keywords: Binding Sites ; Biological Transport, Active ; Escherichia coli Proteins/*chemistry/*metabolism ; Hydrophobic and Hydrophilic Interactions ; Hydroxyl Radical ; Ion Transport ; Kinetics ; Mass Spectrometry ; Membrane Transport Proteins/*chemistry/*metabolism ; Models, Molecular ; Protein Binding ; Protein Conformation ; *Protons ; Pulse Radiolysis ; Water/metabolism ; X-Rays ; Zinc/*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
  • 63
    facet.materialart.
    Unknown
    Structural basis of PAM-dependent target DNA recognition by the Cas9 endonuclease (2014)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2014-08-01
    Description: The CRISPR-associated protein Cas9 is an RNA-guided endonuclease that cleaves double-stranded DNA bearing sequences complementary to a 20-nucleotide segment in the guide RNA. Cas9 has emerged as a versatile molecular tool for genome editing and gene expression control. RNA-guided DNA recognition and cleavage strictly require the presence of a protospacer adjacent motif (PAM) in the target DNA. Here we report a crystal structure of Streptococcus pyogenes Cas9 in complex with a single-molecule guide RNA and a target DNA containing a canonical 5'-NGG-3' PAM. The structure reveals that the PAM motif resides in a base-paired DNA duplex. The non-complementary strand GG dinucleotide is read out via major-groove interactions with conserved arginine residues from the carboxy-terminal domain of Cas9. Interactions with the minor groove of the PAM duplex and the phosphodiester group at the +1 position in the target DNA strand contribute to local strand separation immediately upstream of the PAM. These observations suggest a mechanism for PAM-dependent target DNA melting and RNA-DNA hybrid formation. Furthermore, this study establishes a framework for the rational engineering of Cas9 enzymes with novel PAM specificities.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4176945/" 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/PMC4176945/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Anders, Carolin -- Niewoehner, Ole -- Duerst, Alessia -- Jinek, Martin -- 337284/European Research Council/International -- England -- Nature. 2014 Sep 25;513(7519):569-73. doi: 10.1038/nature13579. Epub 2014 Jul 27.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25079318" target="_blank"〉PubMed〈/a〉
    Keywords: Arginine/genetics/metabolism ; *Base Pairing ; Base Sequence ; CRISPR-Associated Proteins/*metabolism ; Crystallography, X-Ray ; DNA/*chemistry/genetics/*metabolism ; Endonucleases/*metabolism ; Models, Molecular ; Nucleic Acid Denaturation ; *Nucleotide Motifs ; Protein Conformation ; RNA, Guide/chemistry/genetics/metabolism ; Streptococcus pyogenes/*enzymology ; 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
  • 64
    facet.materialart.
    Unknown
    Structure of a lipid-bound extended synaptotagmin indicates a role in lipid transfer (2014)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2014-05-23
    Description: Growing evidence suggests that close appositions between the endoplasmic reticulum (ER) and other membranes, including appositions with the plasma membrane (PM), mediate exchange of lipids between these bilayers. The mechanisms of such exchange, which allows lipid transfer independently of vesicular transport, remain poorly understood. The presence of a synaptotagmin-like mitochondrial-lipid-binding protein (SMP) domain, a proposed lipid-binding module, in several proteins localized at membrane contact sites has raised the possibility that such domains may be implicated in lipid transport. SMP-containing proteins include components of the ERMES complex, an ER-mitochondrial tether, and the extended synaptotagmins (known as tricalbins in yeast), which are ER-PM tethers. Here we present at 2.44 A resolution the crystal structure of a fragment of human extended synaptotagmin 2 (E-SYT2), including an SMP domain and two adjacent C2 domains. The SMP domain has a beta-barrel structure like protein modules in the tubular-lipid-binding (TULIP) superfamily. It dimerizes to form an approximately 90-A-long cylinder traversed by a channel lined entirely with hydrophobic residues, with the two C2A-C2B fragments forming arched structures flexibly linked to the SMP domain. Importantly, structural analysis complemented by mass spectrometry revealed the presence of glycerophospholipids in the E-SYT2 SMP channel, indicating a direct role for E-SYTs in lipid transport. These findings provide strong evidence for a role of SMP-domain-containing proteins in the control of lipid transfer at membrane contact sites and have broad implications beyond the field of ER-to-PM appositions.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4135724/" 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/PMC4135724/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schauder, Curtis M -- Wu, Xudong -- Saheki, Yasunori -- Narayanaswamy, Pradeep -- Torta, Federico -- Wenk, Markus R -- De Camilli, Pietro -- Reinisch, Karin M -- DK082700/DK/NIDDK NIH HHS/ -- GM080616/GM/NIGMS NIH HHS/ -- P30 DA018343/DA/NIDA NIH HHS/ -- R01 DK082700/DK/NIDDK NIH HHS/ -- R01 GM080616/GM/NIGMS NIH HHS/ -- R37 NS036251/NS/NINDS NIH HHS/ -- R37NS36251/NS/NINDS NIH HHS/ -- UL1 TR000142/TR/NCATS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2014 Jun 26;510(7506):552-5.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24847877" target="_blank"〉PubMed〈/a〉
    Keywords: Binding Sites ; Cell Membrane/metabolism ; Crystallography, X-Ray ; Endoplasmic Reticulum/metabolism ; Glycerophospholipids/metabolism ; Humans ; Hydrophobic and Hydrophilic Interactions ; *Lipid Metabolism ; *Lipids ; Mitochondria/metabolism ; Mitochondrial Proteins/chemistry/metabolism ; Models, Molecular ; Protein Conformation ; Protein Multimerization ; Synaptotagmins/*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
  • 65
    facet.materialart.
    Unknown
    Medicine. Combating evolution to fight disease (2014)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2014-03-08
    Description: 〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4117199/" 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/PMC4117199/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rosenberg, Susan M -- Queitsch, Christine -- DP1 CA174424/CA/NCI NIH HHS/ -- DP1-CA174424/CA/NCI NIH HHS/ -- DP2 OD008371/OD/NIH HHS/ -- DP2-OD008371/OD/NIH HHS/ -- R01 CA085777/CA/NCI NIH HHS/ -- R01 GM053158/GM/NIGMS NIH HHS/ -- R01-CA85777/CA/NCI NIH HHS/ -- R01-GM53158/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2014 Mar 7;343(6175):1088-9. doi: 10.1126/science.1247472.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Departments of Molecular and Human Genetics, Biochemistry and Molecular Biology, Molecular Virology and Microbiology, and Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24604189" target="_blank"〉PubMed〈/a〉
    Keywords: Antineoplastic Agents/pharmacology/*therapeutic use ; Biodiversity ; DNA Replication/drug effects ; *Evolution, Molecular ; HSP90 Heat-Shock Proteins/metabolism ; Humans ; Mutagenesis ; Neoplasm Invasiveness ; Neoplasm Metastasis/drug therapy ; Neoplasms/blood supply/*drug therapy/*genetics ; Neovascularization, Pathologic/drug therapy ; 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
  • 66
    facet.materialart.
    Unknown
    Electron microscopy: Ultrastable gold substrates for electron cryomicroscopy (2014)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2014-12-17
    Description: Despite recent advances, the structures of many proteins cannot be determined by electron cryomicroscopy because the individual proteins move during irradiation. This blurs the images so that they cannot be aligned with each other to calculate a three-dimensional density. Much of this movement stems from instabilities in the carbon substrates used to support frozen samples in the microscope. Here we demonstrate a gold specimen support that nearly eliminates substrate motion during irradiation. This increases the subnanometer image contrast such that alpha helices of individual proteins are resolved. With this improvement, we determine the structure of apoferritin, a smooth octahedral shell of alpha-helical subunits that is particularly difficult to solve by electron microscopy. This advance in substrate design will enable the solution of currently intractable protein structures.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4296556/" 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/PMC4296556/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Russo, Christopher J -- Passmore, Lori A -- 261151/European Research Council/International -- MC_U105192715/Medical Research Council/United Kingdom -- U105192715/Medical Research Council/United Kingdom -- New York, N.Y. -- Science. 2014 Dec 12;346(6215):1377-80. doi: 10.1126/science.1259530.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Medical Research Council (MRC) Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK. ; Medical Research Council (MRC) Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK. passmore@mrc-lmb.cam.ac.uk.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25504723" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Apoferritins/*chemistry/*ultrastructure ; Cryoelectron Microscopy/instrumentation/*methods ; Crystallography, X-Ray ; *Gold ; Horses ; Image Processing, Computer-Assisted ; Protein Conformation ; Protein Multimerization ; Protein Structure, Secondary ; Ribosomes/*ultrastructure
    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
  • 67
    facet.materialart.
    Unknown
    Structure of the large ribosomal subunit from human mitochondria (2014)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2014-10-04
    Description: Human mitochondrial ribosomes are highly divergent from all other known ribosomes and are specialized to exclusively translate membrane proteins. They are linked with hereditary mitochondrial diseases and are often the unintended targets of various clinically useful antibiotics. Using single-particle cryogenic electron microscopy, we have determined the structure of its large subunit to 3.4 angstrom resolution, revealing 48 proteins, 21 of which are specific to mitochondria. The structure unveils an adaptation of the exit tunnel for hydrophobic nascent peptides, extensive remodeling of the central protuberance, including recruitment of mitochondrial valine transfer RNA (tRNA(Val)) to play an integral structural role, and changes in the tRNA binding sites related to the unusual characteristics of mitochondrial tRNAs.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4246062/" 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/PMC4246062/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Brown, Alan -- Amunts, Alexey -- Bai, Xiao-chen -- Sugimoto, Yoichiro -- Edwards, Patricia C -- Murshudov, Garib -- Scheres, Sjors H W -- Ramakrishnan, V -- 096570/Wellcome Trust/United Kingdom -- MC_U105184332/Medical Research Council/United Kingdom -- MC_UP_A025_1012/Medical Research Council/United Kingdom -- MC_UP_A025_1013/Medical Research Council/United Kingdom -- WT096570/Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2014 Nov 7;346(6210):718-22. doi: 10.1126/science.1258026. Epub 2014 Oct 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Medical Research Council, Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK. ; Medical Research Council, Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK. ramak@mrc-lmb.cam.ac.uk.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25278503" target="_blank"〉PubMed〈/a〉
    Keywords: Binding Sites ; Cryoelectron Microscopy ; Humans ; Mitochondria/genetics/*metabolism ; Mitochondrial Proteins/chemistry/ultrastructure ; Mutation ; Nucleic Acid Conformation ; Protein Conformation ; RNA, Transfer, Val/analysis/*chemistry ; Ribosome Subunits/*chemistry/genetics/*ultrastructure
    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
  • 68
    facet.materialart.
    Unknown
    SRP RNA remodeling by SRP68 explains its role in protein translocation (2014)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2014-04-05
    Description: The signal recognition particle (SRP) is central to membrane protein targeting; SRP RNA is essential for SRP assembly, elongation arrest, and activation of SRP guanosine triphosphatases. In eukaryotes, SRP function relies on the SRP68-SRP72 heterodimer. We present the crystal structures of the RNA-binding domain of SRP68 (SRP68-RBD) alone and in complex with SRP RNA and SRP19. SRP68-RBD is a tetratricopeptide-like module that binds to a RNA three-way junction, bends the RNA, and inserts an alpha-helical arginine-rich motif (ARM) into the major groove. The ARM opens the conserved 5f RNA loop, which in ribosome-bound SRP establishes a contact to ribosomal RNA. Our data provide the structural basis for eukaryote-specific, SRP68-driven RNA remodeling required for protein translocation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Grotwinkel, Jan Timo -- Wild, Klemens -- Segnitz, Bernd -- Sinning, Irmgard -- New York, N.Y. -- Science. 2014 Apr 4;344(6179):101-4. doi: 10.1126/science.1249094.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Heidelberg University Biochemistry Center (BZH), INF 328, D-69120 Heidelberg, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24700861" target="_blank"〉PubMed〈/a〉
    Keywords: Crystallography, X-Ray ; Humans ; Hydrophobic and Hydrophilic Interactions ; Models, Molecular ; Nucleic Acid Conformation ; Protein Binding ; Protein Conformation ; Protein Multimerization ; Protein Structure, Secondary ; Protein Structure, Tertiary ; *Protein Transport ; RNA, Ribosomal/chemistry/metabolism ; RNA, Small Cytoplasmic/*chemistry/*metabolism ; Ribosomes ; Signal Recognition Particle/*chemistry/genetics/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
  • 69
    facet.materialart.
    Unknown
    Ion permeation in K(+) channels occurs by direct Coulomb knock-on (2014)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2014-10-18
    Description: Potassium channels selectively conduct K(+) ions across cellular membranes with extraordinary efficiency. Their selectivity filter exhibits four binding sites with approximately equal electron density in crystal structures with high K(+) concentrations, previously thought to reflect a superposition of alternating ion- and water-occupied states. Consequently, cotranslocation of ions with water has become a widely accepted ion conduction mechanism for potassium channels. By analyzing more than 1300 permeation events from molecular dynamics simulations at physiological voltages, we observed instead that permeation occurs via ion-ion contacts between neighboring K(+) ions. Coulomb repulsion between adjacent ions is found to be the key to high-efficiency K(+) conduction. Crystallographic data are consistent with directly neighboring K(+) ions in the selectivity filter, and our model offers an intuitive explanation for the high throughput rates of K(+) channels.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kopfer, David A -- Song, Chen -- Gruene, Tim -- Sheldrick, George M -- Zachariae, Ulrich -- de Groot, Bert L -- New York, N.Y. -- Science. 2014 Oct 17;346(6207):352-5. doi: 10.1126/science.1254840.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Biomolecular Dynamics Group, Max Planck Institute for Biophysical Chemistry, 37077 Gottingen, Germany. ; Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UK. sc3210@gmail.com u.zachariae@dundee.ac.uk bgroot@gwdg.de. ; Department of Structural Chemistry, University of Gottingen, 37077 Gottingen, Germany. ; School of Engineering, Physics and Mathematics, University of Dundee, Dundee DD1 4HN, UK. College of Life Sciences, University of Dundee, Dundee DD1 5EH, UK. sc3210@gmail.com u.zachariae@dundee.ac.uk bgroot@gwdg.de. ; Biomolecular Dynamics Group, Max Planck Institute for Biophysical Chemistry, 37077 Gottingen, Germany. sc3210@gmail.com u.zachariae@dundee.ac.uk bgroot@gwdg.de.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25324389" target="_blank"〉PubMed〈/a〉
    Keywords: Bacterial Proteins/*chemistry/metabolism ; Binding Sites ; Crystallography, X-Ray ; Molecular Dynamics Simulation ; Potassium/*metabolism ; Potassium Channels/*chemistry/metabolism ; Protein Conformation ; *Static Electricity ; 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
  • 70
    facet.materialart.
    Unknown
    Evolution of oligomeric state through allosteric pathways that mimic ligand binding (2014)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2014-12-20
    Description: Evolution and design of protein complexes are almost always viewed through the lens of amino acid mutations at protein interfaces. We showed previously that residues not involved in the physical interaction between proteins make important contributions to oligomerization by acting indirectly or allosterically. In this work, we sought to investigate the mechanism by which allosteric mutations act, using the example of the PyrR family of pyrimidine operon attenuators. In this family, a perfectly sequence-conserved helix that forms a tetrameric interface is exposed as solvent-accessible surface in dimeric orthologs. This means that mutations must be acting from a distance to destabilize the interface. We identified 11 key mutations controlling oligomeric state, all distant from the interfaces and outside ligand-binding pockets. Finally, we show that the key mutations introduce conformational changes equivalent to the conformational shift between the free versus nucleotide-bound conformations of the proteins.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4337988/" 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/PMC4337988/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Perica, Tina -- Kondo, Yasushi -- Tiwari, Sandhya P -- McLaughlin, Stephen H -- Kemplen, Katherine R -- Zhang, Xiuwei -- Steward, Annette -- Reuter, Nathalie -- Clarke, Jane -- Teichmann, Sarah A -- 095195/Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2014 Dec 19;346(6216):1254346. doi: 10.1126/science.1254346.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK. Medical Research Council (MRC) Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge CB2 0QH, UK. ; Medical Research Council (MRC) Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge CB2 0QH, UK. ; Department of Molecular Biology, University of Bergen University of Bergen, P.O. Box 7803, N-5020 Bergen, Norway. Computational Biology Unit, Department of Informatics, University of Bergen, P.O. Box 7803, N-5020 Bergen, Norway. ; Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK. ; European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK. ; European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK. saraht@ebi.ac.uk.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25525255" target="_blank"〉PubMed〈/a〉
    Keywords: Allosteric Regulation/*genetics ; Amino Acid Sequence ; Bacillus subtilis/metabolism ; Bacterial Proteins/*chemistry/genetics ; Conserved Sequence ; *Evolution, Molecular ; Ligands ; Mutation ; Pentosyltransferases/*chemistry/genetics ; Protein Binding/genetics ; Protein Conformation ; *Protein Engineering ; Protein Multimerization/*genetics ; Repressor Proteins/*chemistry/genetics
    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
  • 71
    facet.materialart.
    Unknown
    How the ribosome hands the A-site tRNA to the P site during EF-G-catalyzed translocation (2014)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2014-09-06
    Description: Coupled translocation of messenger RNA and transfer RNA (tRNA) through the ribosome, a process catalyzed by elongation factor EF-G, is a crucial step in protein synthesis. The crystal structure of a bacterial translocation complex describes the binding states of two tRNAs trapped in mid-translocation. The deacylated P-site tRNA has moved into a partly translocated pe/E chimeric hybrid state. The anticodon stem-loop of the A-site tRNA is captured in transition toward the 30S P site, while its 3' acceptor end contacts both the A and P loops of the 50S subunit, forming an ap/ap chimeric hybrid state. The structure shows how features of ribosomal RNA rearrange to hand off the A-site tRNA to the P site, revealing an active role for ribosomal RNA in the translocation process.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4242719/" 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/PMC4242719/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhou, Jie -- Lancaster, Laura -- Donohue, John Paul -- Noller, Harry F -- GM-17129/GM/NIGMS NIH HHS/ -- GM59140/GM/NIGMS NIH HHS/ -- R01 GM017129/GM/NIGMS NIH HHS/ -- R01 GM059140/GM/NIGMS NIH HHS/ -- R01 GM105404/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2014 Sep 5;345(6201):1188-91. doi: 10.1126/science.1255030.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Molecular Biology of RNA and Department of Molecular, Cell and Developmental Biology, University of California at Santa Cruz, Santa Cruz, CA 95064, USA. ; Center for Molecular Biology of RNA and Department of Molecular, Cell and Developmental Biology, University of California at Santa Cruz, Santa Cruz, CA 95064, USA. harry@nuvolari.ucsc.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25190797" target="_blank"〉PubMed〈/a〉
    Keywords: Anticodon/chemistry/metabolism ; Binding Sites ; Catalysis ; Crystallography, X-Ray ; Nucleic Acid Conformation ; Peptide Elongation Factor G/*chemistry/metabolism ; Protein Biosynthesis ; Protein Conformation ; RNA, Messenger/*chemistry/metabolism ; RNA, Transfer/*chemistry/metabolism ; Ribosome Subunits, Large, Bacterial/*chemistry/metabolism ; Thermus thermophilus
    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
  • 72
    facet.materialart.
    Unknown
    Crystal structure of a claudin provides insight into the architecture of tight junctions (2014)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2014-04-20
    Description: Tight junctions are cell-cell adhesion structures in epithelial cell sheets that surround organ compartments in multicellular organisms and regulate the permeation of ions through the intercellular space. Claudins are the major constituents of tight junctions and form strands that mediate cell adhesion and function as paracellular barriers. We report the structure of mammalian claudin-15 at a resolution of 2.4 angstroms. The structure reveals a characteristic beta-sheet fold comprising two extracellular segments, which is anchored to a transmembrane four-helix bundle by a consensus motif. Our analyses suggest potential paracellular pathways with distinctive charges on the extracellular surface, providing insight into the molecular basis of ion homeostasis across tight junctions.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Suzuki, Hiroshi -- Nishizawa, Tomohiro -- Tani, Kazutoshi -- Yamazaki, Yuji -- Tamura, Atsushi -- Ishitani, Ryuichiro -- Dohmae, Naoshi -- Tsukita, Sachiko -- Nureki, Osamu -- Fujiyoshi, Yoshinori -- New York, N.Y. -- Science. 2014 Apr 18;344(6181):304-7. doi: 10.1126/science.1248571.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cellular and Structural Physiology Institute, Nagoya University, Chikusa, Nagoya 464-8601, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24744376" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Motifs ; Amino Acid Sequence ; Animals ; Claudins/*chemistry ; Crystallography, X-Ray ; Mice ; Models, Molecular ; Molecular Sequence Data ; Protein Conformation ; Protein Folding ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Protein Subunits/chemistry ; Static Electricity ; Tight Junctions/*chemistry/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
  • 73
    facet.materialart.
    Unknown
    Structure and selectivity in bestrophin ion channels (2014)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2014-10-18
    Description: Human bestrophin-1 (hBest1) is a calcium-activated chloride channel from the retinal pigment epithelium, where mutations are associated with vitelliform macular degeneration, or Best disease. We describe the structure of a bacterial homolog (KpBest) of hBest1 and functional characterizations of both channels. KpBest is a pentamer that forms a five-helix transmembrane pore, closed by three rings of conserved hydrophobic residues, and has a cytoplasmic cavern with a restricted exit. From electrophysiological analysis of structure-inspired mutations in KpBest and hBest1, we find a sensitive control of ion selectivity in the bestrophins, including reversal of anion/cation selectivity, and dramatic activation by mutations at the cytoplasmic exit. A homology model of hBest1 shows the locations of disease-causing mutations and suggests possible roles in regulation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4341822/" 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/PMC4341822/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yang, Tingting -- Liu, Qun -- Kloss, Brian -- Bruni, Renato -- Kalathur, Ravi C -- Guo, Youzhong -- Kloppmann, Edda -- Rost, Burkhard -- Colecraft, Henry M -- Hendrickson, Wayne A -- GM095315/GM/NIGMS NIH HHS/ -- GM107462/GM/NIGMS NIH HHS/ -- R01 GM107462/GM/NIGMS NIH HHS/ -- U54 GM075026/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2014 Oct 17;346(6207):355-9. doi: 10.1126/science.1259723. Epub 2014 Sep 25.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA. ; New York Structural Biology Center, Synchrotron Beamlines, Brookhaven National Laboratory, Upton, NY 11973, USA. ; New York Consortium on Membrane Protein Structure, New York Structural Biology Center, 89 Convent Avenue, New York, NY 10027, USA. ; New York Consortium on Membrane Protein Structure, New York Structural Biology Center, 89 Convent Avenue, New York, NY 10027, USA. Department of Informatics, Bioinformatics and Computational Biology, TUM (Technische Universitat Munchen), Garching 85748, Germany. ; Department of Physiology and Cellular Biophysics, Columbia University, New York, NY 10032, USA. ; Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA. New York Structural Biology Center, Synchrotron Beamlines, Brookhaven National Laboratory, Upton, NY 11973, USA. New York Consortium on Membrane Protein Structure, New York Structural Biology Center, 89 Convent Avenue, New York, NY 10027, USA. Department of Physiology and Cellular Biophysics, Columbia University, New York, NY 10032, USA. wayne@xtl.cumc.columbia.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25324390" target="_blank"〉PubMed〈/a〉
    Keywords: Bacterial Proteins/*chemistry ; Chloride Channels/*chemistry ; Crystallography, X-Ray ; Electric Conductivity ; Eye Proteins/*chemistry ; Humans ; *Klebsiella pneumoniae ; Protein Conformation ; Static Electricity
    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
  • 74
    facet.materialart.
    Unknown
    Crystallography at 100. Going from strength to strength. Introduction (2014)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2014-03-08
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Coontz, Robert -- Fahrenkamp-Uppenbrink, Julia -- Lavine, Marc -- Vinson, Valda -- New York, N.Y. -- Science. 2014 Mar 7;343(6175):1091. doi: 10.1126/science.343.6175.1091.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24604190" target="_blank"〉PubMed〈/a〉
    Keywords: Crystallography, X-Ray/*history/trends ; Databases, Protein ; History, 20th Century ; History, 21st Century ; 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
  • 75
    facet.materialart.
    Unknown
    Time-resolved serial crystallography captures high-resolution intermediates of photoactive yellow protein (2014)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2014-12-06
    Description: Serial femtosecond crystallography using ultrashort pulses from x-ray free electron lasers (XFELs) enables studies of the light-triggered dynamics of biomolecules. We used microcrystals of photoactive yellow protein (a bacterial blue light photoreceptor) as a model system and obtained high-resolution, time-resolved difference electron density maps of excellent quality with strong features; these allowed the determination of structures of reaction intermediates to a resolution of 1.6 angstroms. Our results open the way to the study of reversible and nonreversible biological reactions on time scales as short as femtoseconds under conditions that maximize the extent of reaction initiation throughout the crystal.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4361027/" 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/PMC4361027/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tenboer, Jason -- Basu, Shibom -- Zatsepin, Nadia -- Pande, Kanupriya -- Milathianaki, Despina -- Frank, Matthias -- Hunter, Mark -- Boutet, Sebastien -- Williams, Garth J -- Koglin, Jason E -- Oberthuer, Dominik -- Heymann, Michael -- Kupitz, Christopher -- Conrad, Chelsie -- Coe, Jesse -- Roy-Chowdhury, Shatabdi -- Weierstall, Uwe -- James, Daniel -- Wang, Dingjie -- Grant, Thomas -- Barty, Anton -- Yefanov, Oleksandr -- Scales, Jennifer -- Gati, Cornelius -- Seuring, Carolin -- Srajer, Vukica -- Henning, Robert -- Schwander, Peter -- Fromme, Raimund -- Ourmazd, Abbas -- Moffat, Keith -- Van Thor, Jasper J -- Spence, John C H -- Fromme, Petra -- Chapman, Henry N -- Schmidt, Marius -- P41 GM103543/GM/NIGMS NIH HHS/ -- R01GM095583/GM/NIGMS NIH HHS/ -- R24 GM111072/GM/NIGMS NIH HHS/ -- R24GM111072/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2014 Dec 5;346(6214):1242-6. doi: 10.1126/science.1259357.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Physics Department, University of Wisconsin, Milwaukee, WI 53211, USA. ; Department of Chemistry and Biochemistry, Arizona State University, Tempe, AZ 85287, USA. ; Department of Physics, Arizona State University, Tempe, AZ 85287, USA. ; Linac Coherent Light Source, SLAC National Accelerator Laboratory, Sand Hill Road, Menlo Park, CA 94025, USA. ; Lawrence Livermore National Laboratory, Livermore, CA 94550, USA. ; Centre for Ultrafast Imaging, University of Hamburg, 22761 Hamburg, Germany. ; Center for Free Electron Laser Science, Deutsches Elektronen Synchrotron DESY, Notkestrasse 85, 22607 Hamburg, Germany. ; Hauptman-Woodward Institute, State University of New York at Buffalo, 700 Ellicott Street, Buffalo, NY 14203, USA. ; Centre for Ultrafast Imaging, University of Hamburg, 22761 Hamburg, Germany. Center for Free Electron Laser Science, Deutsches Elektronen Synchrotron DESY, Notkestrasse 85, 22607 Hamburg, Germany. ; Center for Advanced Radiation Sources, University of Chicago, Chicago, IL 60637, USA. ; Center for Advanced Radiation Sources, University of Chicago, Chicago, IL 60637, USA. Department of Biochemistry and Molecular Biology and Institute for Biophysical Dynamics, University of Chicago, Chicago, IL 60637, USA. ; Department of Biochemistry and Molecular Biology and Institute for Biophysical Dynamics, University of Chicago, Chicago, IL 60637, USA. ; Physics Department, University of Wisconsin, Milwaukee, WI 53211, USA. m-schmidt@uwm.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25477465" target="_blank"〉PubMed〈/a〉
    Keywords: Bacterial Proteins/chemistry/*ultrastructure ; Crystallography, X-Ray/*methods ; Photoreceptors, Microbial/chemistry/*ultrastructure ; Protein Conformation ; Time Factors
    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
  • 76
    facet.materialart.
    Unknown
    Complement is activated by IgG hexamers assembled at the cell surface (2014)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2014-03-15
    Description: Complement activation by antibodies bound to pathogens, tumors, and self antigens is a critical feature of natural immune defense, a number of disease processes, and immunotherapies. How antibodies activate the complement cascade, however, is poorly understood. We found that specific noncovalent interactions between Fc segments of immunoglobulin G (IgG) antibodies resulted in the formation of ordered antibody hexamers after antigen binding on cells. These hexamers recruited and activated C1, the first component of complement, thereby triggering the complement cascade. The interactions between neighboring Fc segments could be manipulated to block, reconstitute, and enhance complement activation and killing of target cells, using all four human IgG subclasses. We offer a general model for understanding antibody-mediated complement activation and the design of antibody therapeutics with enhanced efficacy.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4250092/" 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/PMC4250092/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Diebolder, Christoph A -- Beurskens, Frank J -- de Jong, Rob N -- Koning, Roman I -- Strumane, Kristin -- Lindorfer, Margaret A -- Voorhorst, Marleen -- Ugurlar, Deniz -- Rosati, Sara -- Heck, Albert J R -- van de Winkel, Jan G J -- Wilson, Ian A -- Koster, Abraham J -- Taylor, Ronald P -- Saphire, Erica Ollmann -- Burton, Dennis R -- Schuurman, Janine -- Gros, Piet -- Parren, Paul W H I -- AI055332/AI/NIAID NIH HHS/ -- AI084817/AI/NIAID NIH HHS/ -- R01 AI055332/AI/NIAID NIH HHS/ -- R37 AI055332/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2014 Mar 14;343(6176):1260-3. doi: 10.1126/science.1248943.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Crystal and Structural Chemistry, Bijvoet Center for Biomolecular Research, Department of Chemistry, Faculty of Science, Utrecht University, 3584 CH Utrecht, Netherlands.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24626930" target="_blank"〉PubMed〈/a〉
    Keywords: Cell Membrane/*immunology ; *Complement Activation ; Complement C1/*immunology ; Humans ; Immunoglobulin Fab Fragments/chemistry/immunology ; Immunoglobulin G/*chemistry/immunology ; Liposomes ; Protein Conformation ; Protein Multimerization
    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
  • 77
    facet.materialart.
    Unknown
    Biofuels. Engineering alcohol tolerance in yeast (2014)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2014-10-04
    Description: Ethanol toxicity in the yeast Saccharomyces cerevisiae limits titer and productivity in the industrial production of transportation bioethanol. We show that strengthening the opposing potassium and proton electrochemical membrane gradients is a mechanism that enhances general resistance to multiple alcohols. The elevation of extracellular potassium and pH physically bolsters these gradients, increasing tolerance to higher alcohols and ethanol fermentation in commercial and laboratory strains (including a xylose-fermenting strain) under industrial-like conditions. Production per cell remains largely unchanged, with improvements deriving from heightened population viability. Likewise, up-regulation of the potassium and proton pumps in the laboratory strain enhances performance to levels exceeding those of industrial strains. Although genetically complex, alcohol tolerance can thus be dominated by a single cellular process, one controlled by a major physicochemical component but amenable to biological augmentation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4401034/" 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/PMC4401034/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lam, Felix H -- Ghaderi, Adel -- Fink, Gerald R -- Stephanopoulos, Gregory -- R01 GM035010/GM/NIGMS NIH HHS/ -- R01-GM035010/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2014 Oct 3;346(6205):71-5. doi: 10.1126/science.1257859. Epub 2014 Oct 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemical Engineering, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA. Whitehead Institute for Biomedical Research, Cambridge, MA, USA. ; Department of Chemical Engineering, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA. ; Whitehead Institute for Biomedical Research, Cambridge, MA, USA. gfink@wi.mit.edu gregstep@mit.edu. ; Department of Chemical Engineering, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA. gfink@wi.mit.edu gregstep@mit.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25278607" target="_blank"〉PubMed〈/a〉
    Keywords: *Biofuels ; Cation Transport Proteins/genetics ; Cell Culture Techniques ; Cell Membrane/metabolism ; Chemical Engineering ; *Drug Resistance, Fungal/genetics ; Ethanol/*metabolism/pharmacology ; Fermentation ; Genetic Engineering ; Glucose/metabolism ; Hydrogen-Ion Concentration ; Phosphates/*metabolism ; Potassium Compounds/*metabolism ; Proton Pumps/genetics ; Proton-Translocating ATPases/genetics ; Saccharomyces cerevisiae/drug effects/genetics/*metabolism ; Saccharomyces cerevisiae Proteins/genetics ; Up-Regulation ; Xylose/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
  • 78
    facet.materialart.
    Unknown
    Femtosecond crystallography with ultrabright electrons and x-rays: capturing chemistry in action (2014)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2014-03-08
    Description: With the recent advances in ultrabright electron and x-ray sources, it is now possible to extend crystallography to the femtosecond time domain to literally light up atomic motions involved in the primary processes governing structural transitions. This review chronicles the development of brighter and brighter electron and x-ray sources that have enabled atomic resolution to structural dynamics for increasingly complex systems. The primary focus is on achieving sufficient brightness using pump-probe protocols to resolve the far-from-equilibrium motions directing chemical processes that in general lead to irreversible changes in samples. Given the central importance of structural transitions to conceptualizing chemistry, this emerging field has the potential to significantly improve our understanding of chemistry and its connection to driving biological processes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Miller, R J Dwayne -- New York, N.Y. -- Science. 2014 Mar 7;343(6175):1108-16. doi: 10.1126/science.1248488.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Atomically Resolved Dynamics Division, The Max Planck Institute for the Structure and Dynamics of Matter, The Hamburg Centre for Ultrafast Imaging, Luruper Chaussee 149, Hamburg 22761, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24604195" target="_blank"〉PubMed〈/a〉
    Keywords: *Biochemical Processes ; *Chemical Processes ; Crystallography, X-Ray/*methods ; Electrons ; Motion ; Motion Pictures as Topic ; *Photochemical Processes ; Protein Conformation ; Proteins/chemistry ; Time Factors ; X-Rays
    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
  • 79
    facet.materialart.
    Unknown
    The art of entrepreneurship (2014)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2014-11-29
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Langer, Robert S -- Gura, Trisha -- New York, N.Y. -- Science. 2014 Nov 28;346(6213):1146. doi: 10.1126/science.346.6213.1146.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Trisha Gura is a freelance writer who lives in Boston. For more on life and careers visit www.sciencecareers.org.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25430772" target="_blank"〉PubMed〈/a〉
    Keywords: Biotechnology ; *Career Choice ; Chemical Engineering ; *Entrepreneurship ; *Science
    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
  • 80
    facet.materialart.
    Unknown
    A molecular ruler determines the repeat length in eukaryotic cilia and flagella (2014)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2014-11-15
    Description: Existence of cellular structures with specific size raises a fundamental question in biology: How do cells measure length? One conceptual answer to this question is by a molecular ruler, but examples of such rulers in eukaryotes are lacking. In this work, we identified a molecular ruler in eukaryotic cilia and flagella. Using cryo-electron tomography, we found that FAP59 and FAP172 form a 96-nanometer (nm)-long complex in Chlamydomonas flagella and that the absence of the complex disrupted 96-nm repeats of axonemes. Furthermore, lengthening of the FAP59/172 complex by domain duplication resulted in extension of the repeats up to 128 nm, as well as duplication of specific axonemal components. Thus, the FAP59/172 complex is the molecular ruler that determines the 96-nm repeat length and arrangements of components in cilia and flagella.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Oda, Toshiyuki -- Yanagisawa, Haruaki -- Kamiya, Ritsu -- Kikkawa, Masahide -- New York, N.Y. -- Science. 2014 Nov 14;346(6211):857-60. doi: 10.1126/science.1260214.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cell Biology and Anatomy, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo Bunkyo-ku, Tokyo, 113-0033, Japan. ; Department of Biological Science, Graduate School of Science, The University of Tokyo, 7-3-1 Hongo Bunkyo-ku, Tokyo, 113-0033, Japan. Department of Life Science, Faculty of Science, Gakushuin University, 1-5-1 Mejiro, Toshima-ku, Tokyo, 171-8588, Japan. ; Department of Cell Biology and Anatomy, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo Bunkyo-ku, Tokyo, 113-0033, Japan. mkikkawa@m.u-tokyo.ac.jp.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25395538" target="_blank"〉PubMed〈/a〉
    Keywords: Axonemal Dyneins/*chemistry/genetics/ultrastructure ; Chlamydomonas/*physiology/ultrastructure ; Cilia/physiology/ultrastructure ; Eukaryotic Cells/physiology/ultrastructure ; Flagella/*physiology/ultrastructure ; 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
  • 81
    facet.materialart.
    Unknown
    Structure of the mitochondrial translocator protein in complex with a diagnostic ligand (2014)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2014-03-22
    Description: The 18-kilodalton translocator protein TSPO is found in mitochondrial membranes and mediates the import of cholesterol and porphyrins into mitochondria. In line with the role of TSPO in mitochondrial function, TSPO ligands are used for a variety of diagnostic and therapeutic applications in animals and humans. We present the three-dimensional high-resolution structure of mammalian TSPO reconstituted in detergent micelles in complex with its high-affinity ligand PK11195. The TSPO-PK11195 structure is described by a tight bundle of five transmembrane alpha helices that form a hydrophobic pocket accepting PK11195. Ligand-induced stabilization of the structure of TSPO suggests a molecular mechanism for the stimulation of cholesterol transport into mitochondria.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jaremko, Lukasz -- Jaremko, Mariusz -- Giller, Karin -- Becker, Stefan -- Zweckstetter, Markus -- New York, N.Y. -- Science. 2014 Mar 21;343(6177):1363-6. doi: 10.1126/science.1248725.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Max-Planck-Institut fur Biophysikalische Chemie, 37077 Gottingen, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24653034" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Binding Sites ; Biological Transport ; Cholesterol/metabolism ; Hydrophobic and Hydrophilic Interactions ; Isoquinolines/*chemistry/metabolism ; Ligands ; Mice ; Micelles ; Mitochondria/metabolism ; Mitochondrial Membrane Transport Proteins/*chemistry/metabolism ; Models, Molecular ; Molecular Sequence Data ; Nuclear Magnetic Resonance, Biomolecular ; Protein Binding ; Protein Conformation ; Protein Structure, Secondary ; Receptors, GABA/*chemistry/metabolism ; Recombinant Proteins/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
  • 82
    facet.materialart.
    Unknown
    Structural biology scales down (2014)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2014-03-08
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Service, Robert F -- New York, N.Y. -- Science. 2014 Mar 7;343(6175):1072-3, 1075. doi: 10.1126/science.343.6175.1072.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24604178" target="_blank"〉PubMed〈/a〉
    Keywords: Anti-Bacterial Agents/*antagonists & inhibitors/*chemistry/pharmacology ; Budgets ; Crystallography, X-Ray ; *Drug Design ; Financing, Organized ; Molecular Biology/*economics/*trends ; Protein Conformation ; United States ; beta-Lactamases/*chemistry/genetics
    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
  • 83
    facet.materialart.
    Unknown
    Flavivirus NS1 structures reveal surfaces for associations with membranes and the immune system (2014)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2014-02-08
    Description: Flaviviruses, the human pathogens responsible for dengue fever, West Nile fever, tick-borne encephalitis, and yellow fever, are endemic in tropical and temperate parts of the world. The flavivirus nonstructural protein 1 (NS1) functions in genome replication as an intracellular dimer and in immune system evasion as a secreted hexamer. We report crystal structures for full-length, glycosylated NS1 from West Nile and dengue viruses. The NS1 hexamer in crystal structures is similar to a solution hexamer visualized by single-particle electron microscopy. Recombinant NS1 binds to lipid bilayers and remodels large liposomes into lipoprotein nanoparticles. The NS1 structures reveal distinct domains for membrane association of the dimer and interactions with the immune system and are a basis for elucidating the molecular mechanism of NS1 function.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4263348/" 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/PMC4263348/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Akey, David L -- Brown, W Clay -- Dutta, Somnath -- Konwerski, Jamie -- Jose, Joyce -- Jurkiw, Thomas J -- DelProposto, James -- Ogata, Craig M -- Skiniotis, Georgios -- Kuhn, Richard J -- Smith, Janet L -- P01 AI055672/AI/NIAID NIH HHS/ -- P01AI055672/AI/NIAID NIH HHS/ -- Y1-CO-1020/CO/NCI NIH HHS/ -- Y1-GM-1104/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2014 Feb 21;343(6173):881-5. doi: 10.1126/science.1247749. Epub 2014 Feb 6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24505133" target="_blank"〉PubMed〈/a〉
    Keywords: Cell Membrane/chemistry/*virology ; Crystallography, X-Ray ; DEAD-box RNA Helicases/chemistry/immunology ; Humans ; Hydrophobic and Hydrophilic Interactions ; Immune System/chemistry/*virology ; Immunity, Innate ; Lipid Bilayers ; Microscopy, Electron ; Protein Conformation ; Protein Multimerization ; Viral Nonstructural Proteins/*chemistry/immunology
    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
  • 84
    facet.materialart.
    Unknown
    DNA repair. Mechanism of DNA interstrand cross-link processing by repair nuclease FAN1 (2014)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2014-11-29
    Description: DNA interstrand cross-links (ICLs) are highly toxic lesions associated with cancer and degenerative diseases. ICLs can be repaired by the Fanconi anemia (FA) pathway and through FA-independent processes involving the FAN1 nuclease. In this work, FAN1-DNA crystal structures and biochemical data reveal that human FAN1 cleaves DNA successively at every third nucleotide. In vitro, this exonuclease mechanism allows FAN1 to excise an ICL from one strand through flanking incisions. DNA access requires a 5'-terminal phosphate anchor at a nick or a 1- or 2-nucleotide flap and is augmented by a 3' flap, suggesting that FAN1 action is coupled to DNA synthesis or recombination. FAN1's mechanism of ICL excision is well suited for processing other localized DNA adducts as well.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4285437/" 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/PMC4285437/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wang, Renjing -- Persky, Nicole S -- Yoo, Barney -- Ouerfelli, Ouathek -- Smogorzewska, Agata -- Elledge, Stephen J -- Pavletich, Nikola P -- P30 CA008748/CA/NCI NIH HHS/ -- R01 HL120922/HL/NHLBI NIH HHS/ -- R01HL120922/HL/NHLBI NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2014 Nov 28;346(6213):1127-30. doi: 10.1126/science.1258973.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Structural Biology Program and Howard Hughes Medical Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. ; Molecular Pharmacology and Chemistry Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. ; Laboratory of Genome Maintenance, The Rockefeller University, New York, NY 10065, USA. ; Department of Genetics and Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115, USA. Division of Genetics, Brigham and Women's Hospital, Boston, MA 02115, USA. ; Structural Biology Program and Howard Hughes Medical Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. pavletin@mskcc.org.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25430771" target="_blank"〉PubMed〈/a〉
    Keywords: DNA/biosynthesis/*chemistry/genetics ; DNA Adducts/*chemistry/genetics ; *DNA Repair ; DNA Replication ; Exodeoxyribonucleases/*chemistry/genetics ; Humans ; Nucleic Acid Conformation ; Protein Conformation ; Recombination, Genetic
    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
  • 85
    facet.materialart.
    Unknown
    Bacterial cell wall. MurJ is the flippase of lipid-linked precursors for peptidoglycan biogenesis (2014)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2014-07-12
    Description: Peptidoglycan (PG) is a polysaccharide matrix that protects bacteria from osmotic lysis. Inhibition of its biogenesis is a proven strategy for killing bacteria with antibiotics. The assembly of PG requires disaccharide-pentapeptide building blocks attached to a polyisoprene lipid carrier called lipid II. Although the stages of lipid II synthesis are known, the identity of the essential flippase that translocates it across the cytoplasmic membrane for PG polymerization is unclear. We developed an assay for lipid II flippase activity and used a chemical genetic strategy to rapidly and specifically block flippase function. We combined these approaches to demonstrate that MurJ is the lipid II flippase in Escherichia coli.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4163187/" 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/PMC4163187/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sham, Lok-To -- Butler, Emily K -- Lebar, Matthew D -- Kahne, Daniel -- Bernhardt, Thomas G -- Ruiz, Natividad -- F32 GM103056/GM/NIGMS NIH HHS/ -- F32GM103056/GM/NIGMS NIH HHS/ -- R01 AI099144/AI/NIAID NIH HHS/ -- R01 GM076710/GM/NIGMS NIH HHS/ -- R01 GM100951/GM/NIGMS NIH HHS/ -- R01AI099144/AI/NIAID NIH HHS/ -- R01GM100951/GM/NIGMS NIH HHS/ -- R01GM76710/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2014 Jul 11;345(6193):220-2. doi: 10.1126/science.1254522.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA. ; Department of Microbiology, Ohio State University, Columbus, OH 43210, USA. ; Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA. ; Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA. Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA. ; Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA. thomas_bernhardt@hms.harvard.edu ruiz.82@osu.edu. ; Department of Microbiology, Ohio State University, Columbus, OH 43210, USA. thomas_bernhardt@hms.harvard.edu ruiz.82@osu.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25013077" target="_blank"〉PubMed〈/a〉
    Keywords: Cell Wall/*metabolism ; Escherichia coli/genetics/*metabolism ; Escherichia coli Proteins/antagonists & inhibitors/chemistry/*physiology ; Mesylates/pharmacology ; Models, Molecular ; Peptidoglycan/*biosynthesis/chemistry ; Phospholipid Transfer Proteins/antagonists & inhibitors/chemistry/*physiology ; Protein Conformation ; Uridine Diphosphate N-Acetylmuramic Acid/*analogs & derivatives/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
  • 86
    facet.materialart.
    Unknown
    Crystal structure of the human OX2 orexin receptor bound to the insomnia drug suvorexant (2014)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2014-12-24
    Description: The orexin (also known as hypocretin) G protein-coupled receptors (GPCRs) respond to orexin neuropeptides in the central nervous system to regulate sleep and other behavioural functions in humans. Defects in orexin signalling are responsible for the human diseases of narcolepsy and cataplexy; inhibition of orexin receptors is an effective therapy for insomnia. The human OX2 receptor (OX2R) belongs to the beta branch of the rhodopsin family of GPCRs, and can bind to diverse compounds including the native agonist peptides orexin-A and orexin-B and the potent therapeutic inhibitor suvorexant. Here, using lipid-mediated crystallization and protein engineering with a novel fusion chimaera, we solved the structure of the human OX2R bound to suvorexant at 2.5 A resolution. The structure reveals how suvorexant adopts a pi-stacked horseshoe-like conformation and binds to the receptor deep in the orthosteric pocket, stabilizing a network of extracellular salt bridges and blocking transmembrane helix motions necessary for activation. Computational docking suggests how other classes of synthetic antagonists may interact with the receptor at a similar position in an analogous pi-stacked fashion. Elucidation of the molecular architecture of the human OX2R expands our understanding of peptidergic GPCR ligand recognition and will aid further efforts to modulate orexin signalling for therapeutic ends.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yin, Jie -- Mobarec, Juan Carlos -- Kolb, Peter -- Rosenbaum, Daniel M -- England -- Nature. 2015 Mar 12;519(7542):247-50. doi: 10.1038/nature14035. Epub 2014 Dec 22.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biophysics, The University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA. ; Department of Pharmaceutical Chemistry, Philipps-University Marburg, 35032 Marburg, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25533960" target="_blank"〉PubMed〈/a〉
    Keywords: Azepines/*chemistry/metabolism/*pharmacology ; Crystallography, X-Ray ; Humans ; Molecular Docking Simulation ; *Orexin Receptor Antagonists ; Orexin Receptors/*chemistry/metabolism ; Protein Conformation ; Receptors, G-Protein-Coupled/antagonists & inhibitors/chemistry/metabolism ; Recombinant Fusion Proteins/chemistry/metabolism ; Sleep Initiation and Maintenance Disorders/drug therapy ; Triazoles/*chemistry/metabolism/*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
  • 87
    facet.materialart.
    Unknown
    A human tRNA synthetase is a potent PARP1-activating effector target for resveratrol (2014)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2014-12-24
    Description: Resveratrol is reported to extend lifespan and provide cardio-neuro-protective, anti-diabetic, and anti-cancer effects by initiating a stress response that induces survival genes. Because human tyrosyl transfer-RNA (tRNA) synthetase (TyrRS) translocates to the nucleus under stress conditions, we considered the possibility that the tyrosine-like phenolic ring of resveratrol might fit into the active site pocket to effect a nuclear role. Here we present a 2.1 A co-crystal structure of resveratrol bound to the active site of TyrRS. Resveratrol nullifies the catalytic activity and redirects TyrRS to a nuclear function, stimulating NAD(+)-dependent auto-poly-ADP-ribosylation of poly(ADP-ribose) polymerase 1 (PARP1). Downstream activation of key stress signalling pathways are causally connected to TyrRS-PARP1-NAD(+) collaboration. This collaboration is also demonstrated in the mouse, and is specifically blocked in vivo by a resveratrol-displacing tyrosyl adenylate analogue. In contrast to functionally diverse tRNA synthetase catalytic nulls created by alternative splicing events that ablate active sites, here a non-spliced TyrRS catalytic null reveals a new PARP1- and NAD(+)-dependent dimension to the physiological mechanism of resveratrol.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4368482/" 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/PMC4368482/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sajish, Mathew -- Schimmel, Paul -- CA92577/CA/NCI NIH HHS/ -- R01 CA092577/CA/NCI NIH HHS/ -- England -- Nature. 2015 Mar 19;519(7543):370-3. doi: 10.1038/nature14028. Epub 2014 Dec 22.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Skaggs Institute for Chemical Biology, The Scripps Laboratories for tRNA Synthetase Research, Department of Molecular and Cell Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA. ; 1] The Skaggs Institute for Chemical Biology, The Scripps Laboratories for tRNA Synthetase Research, Department of Molecular and Cell Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA [2] The Scripps Florida Research Institute, 130 Scripps Way, Jupiter, Florida 33458, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25533949" target="_blank"〉PubMed〈/a〉
    Keywords: Alternative Splicing ; Animals ; Biocatalysis/drug effects ; Catalytic Domain ; Cell Nucleus/enzymology ; Crystallography, X-Ray ; Culture Media, Serum-Free ; Enzyme Activation/drug effects ; Humans ; Male ; Mice ; Mice, Inbred BALB C ; Models, Molecular ; Poly Adenosine Diphosphate Ribose/metabolism ; Poly(ADP-ribose) Polymerases/chemistry/*metabolism ; Protein Conformation ; Signal Transduction/drug effects ; Sirtuin 1/metabolism ; Sirtuins/metabolism ; Stilbenes/antagonists & inhibitors/chemistry/*pharmacology ; Tyrosine-tRNA Ligase/*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
  • 88
    facet.materialart.
    Unknown
    Genetic and molecular basis of drug resistance and species-specific drug action in schistosome parasites (2013)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2013-11-23
    Description: Oxamniquine resistance evolved in the human blood fluke (Schistosoma mansoni) in Brazil in the 1970s. We crossed parental parasites differing ~500-fold in drug response, determined drug sensitivity and marker segregation in clonally derived second-generation progeny, and identified a single quantitative trait locus (logarithm of odds = 31) on chromosome 6. A sulfotransferase was identified as the causative gene by using RNA interference knockdown and biochemical complementation assays, and we subsequently demonstrated independent origins of loss-of-function mutations in field-derived and laboratory-selected resistant parasites. These results demonstrate the utility of linkage mapping in a human helminth parasite, while crystallographic analyses of protein-drug interactions illuminate the mode of drug action and provide a framework for rational design of oxamniquine derivatives that kill both S. mansoni and S. haematobium, the two species responsible for 〉99% of schistosomiasis cases worldwide.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4136436/" 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/PMC4136436/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Valentim, Claudia L L -- Cioli, Donato -- Chevalier, Frederic D -- Cao, Xiaohang -- Taylor, Alexander B -- Holloway, Stephen P -- Pica-Mattoccia, Livia -- Guidi, Alessandra -- Basso, Annalisa -- Tsai, Isheng J -- Berriman, Matthew -- Carvalho-Queiroz, Claudia -- Almeida, Marcio -- Aguilar, Hector -- Frantz, Doug E -- Hart, P John -- LoVerde, Philip T -- Anderson, Timothy J C -- 098051/Wellcome Trust/United Kingdom -- 5R21-AI072704/AI/NIAID NIH HHS/ -- 5R21-AI096277/AI/NIAID NIH HHS/ -- C06 RR013556/RR/NCRR NIH HHS/ -- HHSN272201000005I/PHS HHS/ -- R01 AI097576/AI/NIAID NIH HHS/ -- R01-AI097576/AI/NIAID NIH HHS/ -- R21 AI072704/AI/NIAID NIH HHS/ -- R21 AI096277/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2013 Dec 13;342(6164):1385-9. doi: 10.1126/science.1243106. Epub 2013 Nov 21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Departments of Biochemistry and Pathology, University of Texas Health Science Center, San Antonio, TX 78229, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24263136" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Drug Resistance/*genetics ; Gene Knockdown Techniques ; Genetic Linkage ; Helminth Proteins/*genetics ; Humans ; Molecular Sequence Data ; Mutation ; Oxamniquine/*pharmacology ; Phylogeny ; Protein Conformation ; Quantitative Trait Loci ; RNA Interference ; Schistosoma mansoni/*drug effects/*genetics ; Schistosomicides/*pharmacology ; Sulfotransferases/chemistry/classification/*genetics
    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
    FtsZ protofilaments use a hinge-opening mechanism for constrictive force generation (2013)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2013-07-28
    Description: The essential bacterial protein FtsZ is a guanosine triphosphatase that self-assembles into a structure at the division site termed the "Z ring". During cytokinesis, the Z ring exerts a constrictive force on the membrane by using the chemical energy of guanosine triphosphate hydrolysis. However, the structural basis of this constriction remains unresolved. Here, we present the crystal structure of a guanosine diphosphate-bound Mycobacterium tuberculosis FtsZ protofilament, which exhibits a curved conformational state. The structure reveals a longitudinal interface that is important for function. The protofilament curvature highlights a hydrolysis-dependent conformational switch at the T3 loop that leads to longitudinal bending between subunits, which could generate sufficient force to drive cytokinesis.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3816583/" 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/PMC3816583/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Li, Ying -- Hsin, Jen -- Zhao, Lingyun -- Cheng, Yiwen -- Shang, Weina -- Huang, Kerwyn Casey -- Wang, Hong-Wei -- Ye, Sheng -- 1F32GM100677-01A1/GM/NIGMS NIH HHS/ -- DP2 OD006466/OD/NIH HHS/ -- DP2OD006466/OD/NIH HHS/ -- F32 GM100677/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2013 Jul 26;341(6144):392-5. doi: 10.1126/science.1239248.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Life Sciences Institute, Zhejiang University, Hangzhou, 310058 Zhejiang, P.R. China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23888039" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Bacterial Proteins/*chemistry/genetics/*metabolism ; Cell Membrane/physiology ; Crystallography, X-Ray ; *Cytokinesis ; Cytoskeletal Proteins/*chemistry/genetics/*metabolism ; Escherichia coli/chemistry ; Guanosine Diphosphate/chemistry/metabolism ; Guanosine Triphosphate/metabolism ; Hydrolysis ; Hydrophobic and Hydrophilic Interactions ; Models, Molecular ; Molecular Dynamics Simulation ; Molecular Sequence Data ; Mycobacterium tuberculosis/*chemistry/physiology ; Point Mutation ; Protein Conformation ; Protein Multimerization ; Protein Subunits/chemistry/metabolism ; Staphylococcus aureus/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
  • 90
    facet.materialart.
    Unknown
    Architecture of an RNA polymerase II transcription pre-initiation complex (2013)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2013-09-28
    Description: The protein density and arrangement of subunits of a complete, 32-protein, RNA polymerase II (pol II) transcription pre-initiation complex (PIC) were determined by means of cryogenic electron microscopy and a combination of chemical cross-linking and mass spectrometry. The PIC showed a marked division in two parts, one containing all the general transcription factors (GTFs) and the other pol II. Promoter DNA was associated only with the GTFs, suspended above the pol II cleft and not in contact with pol II. This structural principle of the PIC underlies its conversion to a transcriptionally active state; the PIC is poised for the formation of a transcription bubble and descent of the DNA into the pol II cleft.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4039082/" 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/PMC4039082/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Murakami, Kenji -- Elmlund, Hans -- Kalisman, Nir -- Bushnell, David A -- Adams, Christopher M -- Azubel, Maia -- Elmlund, Dominika -- Levi-Kalisman, Yael -- Liu, Xin -- Gibbons, Brian J -- Levitt, Michael -- Kornberg, Roger D -- AI21144/AI/NIAID NIH HHS/ -- GM063817/GM/NIGMS NIH HHS/ -- GM49885/GM/NIGMS NIH HHS/ -- R01 AI021144/AI/NIAID NIH HHS/ -- R01 GM036659/GM/NIGMS NIH HHS/ -- R01 GM063817/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2013 Nov 8;342(6159):1238724. doi: 10.1126/science.1238724. Epub 2013 Sep 26.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Structural Biology, Stanford University, Stanford, CA 94305, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24072820" target="_blank"〉PubMed〈/a〉
    Keywords: Cryoelectron Microscopy ; DNA, Fungal/chemistry/genetics ; *Gene Expression Regulation, Fungal ; Multiprotein Complexes/*chemistry ; Nucleic Acid Conformation ; Protein Conformation ; RNA Polymerase II/*chemistry ; Saccharomyces cerevisiae/*enzymology/genetics ; Saccharomyces cerevisiae Proteins/*chemistry ; Transcription Factors, General/*chemistry ; *Transcription Initiation, Genetic
    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
    2013 Runners-Up. In vaccine design, looks do matter (2013)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2013-12-21
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉New York, N.Y. -- Science. 2013 Dec 20;342(6165):1442-3. doi: 10.1126/science.342.6165.1442-a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24357293" target="_blank"〉PubMed〈/a〉
    Keywords: Antibodies, Viral/chemistry/immunology ; *Drug Design ; Humans ; Infant ; Protein Conformation ; Protein Engineering ; Respiratory Syncytial Virus Infections/*prevention & control ; Respiratory Syncytial Virus Vaccines/*chemistry/immunology ; Respiratory Syncytial Viruses/*chemistry/immunology ; Viral Fusion Proteins/*chemistry/immunology ; X-Ray Diffraction
    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
    Biochemistry. Integrative structural biology (2013)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2013-02-23
    Description: 〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3633482/" 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/PMC3633482/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ward, Andrew B -- Sali, Andrej -- Wilson, Ian A -- P01 AI082362/AI/NIAID NIH HHS/ -- U54 GM094586/GM/NIGMS NIH HHS/ -- UM1 AI100663/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2013 Feb 22;339(6122):913-5. doi: 10.1126/science.1228565.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Integrative Structural and Computational Biology, International AIDS Vaccine Initiative Neutralizing Antibody Center, Scripps Research Institute, La Jolla, CA 92037, USA. abward@scripps.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23430643" target="_blank"〉PubMed〈/a〉
    Keywords: Algorithms ; Bacterial Secretion Systems ; Biochemistry/*methods ; Chromatin/chemistry ; Computational Biology ; Macromolecular Substances/*chemistry ; *Models, Molecular ; Molecular Biology/*methods ; Molecular Structure ; Multiprotein Complexes/*chemistry ; Proteasome Endopeptidase Complex/chemistry ; Protein Conformation ; Proteins/*chemistry ; Software
    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
    Phycobilisomes supply excitations to both photosystems in a megacomplex in cyanobacteria (2013)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2013-11-30
    Description: In photosynthetic organisms, photons are captured by light-harvesting antenna complexes, and energy is transferred to reaction centers where photochemical reactions take place. We describe here the isolation and characterization of a fully functional megacomplex composed of a phycobilisome antenna complex and photosystems I and II from the cyanobacterium Synechocystis PCC 6803. A combination of in vivo protein cross-linking, mass spectrometry, and time-resolved spectroscopy indicates that the megacomplex is organized to facilitate energy transfer but not intercomplex electron transfer, which requires diffusible intermediates and the cytochrome b6f complex. The organization provides a basis for understanding how phycobilisomes transfer excitation energy to reaction centers and how the energy balance of two photosystems is achieved, allowing the organism to adapt to varying ecophysiological conditions.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3947847/" 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/PMC3947847/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Liu, Haijun -- Zhang, Hao -- Niedzwiedzki, Dariusz M -- Prado, Mindy -- He, Guannan -- Gross, Michael L -- Blankenship, Robert E -- 8 P41 GM103422-35/GM/NIGMS NIH HHS/ -- P41 GM103422/GM/NIGMS NIH HHS/ -- P41 RR000954/RR/NCRR NIH HHS/ -- New York, N.Y. -- Science. 2013 Nov 29;342(6162):1104-7. doi: 10.1126/science.1242321.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, Washington University in St. Louis, St. Louis, MO 63130, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24288334" target="_blank"〉PubMed〈/a〉
    Keywords: Cross-Linking Reagents/chemistry ; Energy Transfer ; Fluorescence ; *Photosynthesis ; Photosystem I Protein Complex/*chemistry/genetics/isolation & purification ; Photosystem II Protein Complex/*chemistry/genetics/isolation & purification ; Phycobilisomes/*chemistry/genetics/isolation & purification ; Protein Conformation ; Synechocystis/*enzymology
    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
    Structural systems biology evaluation of metabolic thermotolerance in Escherichia coli (2013)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2013-06-08
    Description: Genome-scale network reconstruction has enabled predictive modeling of metabolism for many systems. Traditionally, protein structural information has not been represented in such reconstructions. Expansion of a genome-scale model of Escherichia coli metabolism by including experimental and predicted protein structures enabled the analysis of protein thermostability in a network context. This analysis allowed the prediction of protein activities that limit network function at superoptimal temperatures and mechanistic interpretations of mutations found in strains adapted to heat. Predicted growth-limiting factors for thermotolerance were validated through nutrient supplementation experiments and defined metabolic sensitivities to heat stress, providing evidence that metabolic enzyme thermostability is rate-limiting at superoptimal temperatures. Inclusion of structural information expanded the content and predictive capability of genome-scale metabolic networks that enable structural systems biology of metabolism.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3777776/" 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/PMC3777776/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chang, Roger L -- Andrews, Kathleen -- Kim, Donghyuk -- Li, Zhanwen -- Godzik, Adam -- Palsson, Bernhard O -- R01 GM057089/GM/NIGMS NIH HHS/ -- R01 GM101457/GM/NIGMS NIH HHS/ -- R01GM101457/GM/NIGMS NIH HHS/ -- U54 GM094586/GM/NIGMS NIH HHS/ -- U54GM094586/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2013 Jun 7;340(6137):1220-3. doi: 10.1126/science.1234012.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Bioinformatics and Systems Biology Graduate Program, University of California San Diego, La Jolla, CA 92093-0412, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23744946" target="_blank"〉PubMed〈/a〉
    Keywords: Escherichia coli/*genetics/growth & development/*metabolism ; Escherichia coli Proteins/chemistry/genetics/*metabolism ; Gene Expression Regulation, Bacterial ; *Hot Temperature ; *Metabolic Networks and Pathways ; Models, Biological ; Protein Conformation ; Systems Biology ; Transcriptional Activation
    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
    Biochemistry. Have your PIC! (2013)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2013-11-10
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Malik, Sohail -- Roeder, Robert G -- New York, N.Y. -- Science. 2013 Nov 8;342(6159):706-7. doi: 10.1126/science.1246170.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Biochemistry and Molecular Biology, Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24202169" target="_blank"〉PubMed〈/a〉
    Keywords: Catalytic Domain ; Cryoelectron Microscopy ; Crystallography ; DNA/*chemistry ; Humans ; *Promoter Regions, Genetic ; Protein Conformation ; RNA Polymerase II/*chemistry ; Transcription Factors, General/*chemistry ; *Transcription Initiation, Genetic
    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. Structural MS pulls its weight (2013)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2013-06-01
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sharon, Michal -- New York, N.Y. -- Science. 2013 May 31;340(6136):1059-60. doi: 10.1126/science.1236303.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biological Chemistry, Weizmann Institute of Science, Rehovot, Israel. michal.sharon@weizmann.ac.il〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23723227" target="_blank"〉PubMed〈/a〉
    Keywords: Crystallography, X-Ray ; Mass Spectrometry/*methods ; Microscopy, Electron ; Nuclear Magnetic Resonance, Biomolecular ; Protein Conformation ; 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
  • 97
    facet.materialart.
    Unknown
    Structures and receptor binding of hemagglutinins from human-infecting H7N9 influenza viruses (2013)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2013-09-07
    Description: An avian-origin human-infecting influenza (H7N9) virus was recently identified in China. We have evaluated the viral hemagglutinin (HA) receptor-binding properties of two human H7N9 isolates, A/Shanghai/1/2013 (SH-H7N9) (containing the avian-signature residue Gln(226)) and A/Anhui/1/2013 (AH-H7N9) (containing the mammalian-signature residue Leu(226)). We found that SH-H7N9 HA preferentially binds the avian receptor analog, whereas AH-H7N9 HA binds both avian and human receptor analogs. Furthermore, an AH-H7N9 mutant HA (Leu(226) --〉 Gln) was found to exhibit dual receptor-binding property, indicating that other amino acid substitutions contribute to the receptor-binding switch. The structures of SH-H7N9 HA, AH-H7N9 HA, and its mutant in complex with either avian or human receptor analogs show how AH-H7N9 can bind human receptors while still retaining the avian receptor-binding property.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shi, Yi -- Zhang, Wei -- Wang, Fei -- Qi, Jianxun -- Wu, Ying -- Song, Hao -- Gao, Feng -- Bi, Yuhai -- Zhang, Yanfang -- Fan, Zheng -- Qin, Chengfeng -- Sun, Honglei -- Liu, Jinhua -- Haywood, Joel -- Liu, Wenjun -- Gong, Weimin -- Wang, Dayan -- Shu, Yuelong -- Wang, Yu -- Yan, Jinghua -- Gao, George F -- New York, N.Y. -- Science. 2013 Oct 11;342(6155):243-7. doi: 10.1126/science.1242917. Epub 2013 Sep 5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Research Network of Immunity and Health, Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing, China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24009358" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Birds ; Crystallography, X-Ray ; Glycine/chemistry/genetics/metabolism ; Hemagglutinin Glycoproteins, Influenza Virus/*chemistry/metabolism ; Humans ; Influenza A virus/*metabolism ; Influenza in Birds/*virology ; Influenza, Human/*virology ; Protein Conformation ; Receptors, Cell Surface/*chemistry/genetics/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
  • 98
    facet.materialart.
    Unknown
    Geometric catalysis of membrane fission driven by flexible dynamin rings (2013)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2013-03-23
    Description: Biological membrane fission requires protein-driven stress. The guanosine triphosphatase (GTPase) dynamin builds up membrane stress by polymerizing into a helical collar that constricts the neck of budding vesicles. How this curvature stress mediates nonleaky membrane remodeling is actively debated. Using lipid nanotubes as substrates to directly measure geometric intermediates of the fission pathway, we found that GTP hydrolysis limits dynamin polymerization into short, metastable collars that are optimal for fission. Collars as short as two rungs translated radial constriction to reversible hemifission via membrane wedging of the pleckstrin homology domains (PHDs) of dynamin. Modeling revealed that tilting of the PHDs to conform with membrane deformations creates the low-energy pathway for hemifission. This local coordination of dynamin and lipids suggests how membranes can be remodeled in cells.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3980720/" 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/PMC3980720/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shnyrova, Anna V -- Bashkirov, Pavel V -- Akimov, Sergey A -- Pucadyil, Thomas J -- Zimmerberg, Joshua -- Schmid, Sandra L -- Frolov, Vadim A -- GM42455/GM/NIGMS NIH HHS/ -- R01 GM042455/GM/NIGMS NIH HHS/ -- Intramural NIH HHS/ -- New York, N.Y. -- Science. 2013 Mar 22;339(6126):1433-6. doi: 10.1126/science.1233920.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Biophysics Unit (CSIC, UPV/EHU) and Department of Biochemistry and Molecular Biology, University of the Basque Country, Leioa, Spain.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23520112" target="_blank"〉PubMed〈/a〉
    Keywords: Biocatalysis ; Dynamin I/*chemistry/*metabolism ; Guanosine Triphosphate/metabolism ; Hydrolysis ; Lipid Bilayers/chemistry/*metabolism ; Models, Biological ; Nanotubes ; Protein Conformation ; Protein Multimerization ; Protein Structure, Tertiary ; Thermodynamics
    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
    Structural basis for molecular recognition at serotonin receptors (2013)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2013-03-23
    Description: Serotonin or 5-hydroxytryptamine (5-HT) regulates a wide spectrum of human physiology through the 5-HT receptor family. We report the crystal structures of the human 5-HT1B G protein-coupled receptor bound to the agonist antimigraine medications ergotamine and dihydroergotamine. The structures reveal similar binding modes for these ligands, which occupy the orthosteric pocket and an extended binding pocket close to the extracellular loops. The orthosteric pocket is formed by residues conserved in the 5-HT receptor family, clarifying the family-wide agonist activity of 5-HT. Compared with the structure of the 5-HT2B receptor, the 5-HT1B receptor displays a 3 angstrom outward shift at the extracellular end of helix V, resulting in a more open extended pocket that explains subtype selectivity. Together with docking and mutagenesis studies, these structures provide a comprehensive structural basis for understanding receptor-ligand interactions and designing subtype-selective serotonergic drugs.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3644373/" 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/PMC3644373/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wang, Chong -- Jiang, Yi -- Ma, Jinming -- Wu, Huixian -- Wacker, Daniel -- Katritch, Vsevolod -- Han, Gye Won -- Liu, Wei -- Huang, Xi-Ping -- Vardy, Eyal -- McCorvy, John D -- Gao, Xiang -- Zhou, X Edward -- Melcher, Karsten -- Zhang, Chenghai -- Bai, Fang -- Yang, Huaiyu -- Yang, Linlin -- Jiang, Hualiang -- Roth, Bryan L -- Cherezov, Vadim -- Stevens, Raymond C -- Xu, H Eric -- P50 GM073197/GM/NIGMS NIH HHS/ -- R01 DA027170/DA/NIDA NIH HHS/ -- R01 DA27170/DA/NIDA NIH HHS/ -- R01 DK071662/DK/NIDDK NIH HHS/ -- R01 MH061887/MH/NIMH NIH HHS/ -- R01 MH61887/MH/NIMH NIH HHS/ -- U19 MH082441/MH/NIMH NIH HHS/ -- U19 MH82441/MH/NIMH NIH HHS/ -- U54 GM094618/GM/NIGMS NIH HHS/ -- Y1-CO-1020/CO/NCI NIH HHS/ -- Y1-GM-1104/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2013 May 3;340(6132):610-4. doi: 10.1126/science.1232807. Epub 2013 Mar 21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Integrative Structural and Computational Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23519210" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Binding Sites ; Crystallography, X-Ray ; Dihydroergotamine/chemistry/*metabolism ; Ergotamine/chemistry/*metabolism ; Humans ; Hydrogen Bonding ; Hydrophobic and Hydrophilic Interactions ; Ligands ; Lysergic Acid Diethylamide/chemistry/metabolism ; Models, Molecular ; Molecular Docking Simulation ; Molecular Sequence Data ; Mutagenesis ; Norfenfluramine/chemistry/metabolism ; Pindolol/analogs & derivatives/chemistry/metabolism ; Propranolol/chemistry/metabolism ; Protein Conformation ; Protein Folding ; Protein Structure, Secondary ; Receptor, Serotonin, 5-HT1B/*chemistry/genetics/*metabolism ; Serotonin 5-HT1 Receptor Agonists/*chemistry/*metabolism ; Tryptamines/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
  • 100
    facet.materialart.
    Unknown
    Crystal structure of MraY, an essential membrane enzyme for bacterial cell wall synthesis (2013)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2013-08-31
    Description: MraY (phospho-MurNAc-pentapeptide translocase) is an integral membrane enzyme that catalyzes an essential step of bacterial cell wall biosynthesis: the transfer of the peptidoglycan precursor phospho-MurNAc-pentapeptide to the lipid carrier undecaprenyl phosphate. MraY has long been considered a promising target for the development of antibiotics, but the lack of a structure has hindered mechanistic understanding of this critical enzyme and the enzyme superfamily in general. The superfamily includes enzymes involved in bacterial lipopolysaccharide/teichoic acid formation and eukaryotic N-linked glycosylation, modifications that are central in many biological processes. We present the crystal structure of MraY from Aquifex aeolicus (MraYAA) at 3.3 A resolution, which allows us to visualize the overall architecture, locate Mg(2+) within the active site, and provide a structural basis of catalysis for this class of enzyme.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3906829/" 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/PMC3906829/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chung, Ben C -- Zhao, Jinshi -- Gillespie, Robert A -- Kwon, Do-Yeon -- Guan, Ziqiang -- Hong, Jiyong -- Zhou, Pei -- Lee, Seok-Yong -- AI-55588/AI/NIAID NIH HHS/ -- GM-069338/GM/NIGMS NIH HHS/ -- GM-51310/GM/NIGMS NIH HHS/ -- R01 AI055588/AI/NIAID NIH HHS/ -- R01 GM051310/GM/NIGMS NIH HHS/ -- R01 GM100984/GM/NIGMS NIH HHS/ -- U54 GM069338/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2013 Aug 30;341(6149):1012-6. doi: 10.1126/science.1236501.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, Duke University Medical Center, Durham, NC 27710, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23990562" target="_blank"〉PubMed〈/a〉
    Keywords: Bacteria/*enzymology ; Bacterial Proteins/*chemistry/genetics ; Catalytic Domain ; Cell Wall/*chemistry/enzymology ; Crystallography, X-Ray ; Cytoplasm/enzymology ; Membrane Proteins/*chemistry/genetics ; Periplasm/enzymology ; Protein Conformation ; Protein Structure, Secondary ; Transferases/*chemistry/genetics
    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...