ALBERT

All Library Books, journals and Electronic Records Telegrafenberg

Your email was sent successfully. Check your inbox.

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

Proceed reservation?

Export
Filter
  • Models, Molecular  (1,233)
  • American Association for the Advancement of Science (AAAS)  (1,233)
  • American Association of Petroleum Geologists (AAPG)
Collection
Keywords
Publisher
  • American Association for the Advancement of Science (AAAS)  (1,233)
  • American Association of Petroleum Geologists (AAPG)
  • Nature Publishing Group (NPG)  (762)
  • 1
    Publication Date: 2016-03-12
    Description: AMPA-type glutamate receptors (AMPARs), which are central mediators of rapid neurotransmission and synaptic plasticity, predominantly exist as heteromers of the subunits GluA1 to GluA4. Here we report the first AMPAR heteromer structures, which deviate substantially from existing GluA2 homomer structures. Crystal structures of the GluA2/3 and GluA2/4 N-terminal domains reveal a novel compact conformation with an alternating arrangement of the four subunits around a central axis. This organization is confirmed by cysteine cross-linking in full-length receptors, and it permitted us to determine the structure of an intact GluA2/3 receptor by cryogenic electron microscopy. Two models in the ligand-free state, at resolutions of 8.25 and 10.3 angstroms, exhibit substantial vertical compression and close associations between domain layers, reminiscent of N-methyl-D-aspartate receptors. Model 1 resembles a resting state and model 2 a desensitized state, thus providing snapshots of gating transitions in the nominal absence of ligand. Our data reveal organizational features of heteromeric AMPARs and provide a framework to decipher AMPAR architecture and signaling.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4852135/" 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/PMC4852135/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Herguedas, Beatriz -- Garcia-Nafria, Javier -- Cais, Ondrej -- Fernandez-Leiro, Rafael -- Krieger, James -- Ho, Hinze -- Greger, Ingo H -- MC_U105174197/Medical Research Council/United Kingdom -- New York, N.Y. -- Science. 2016 Apr 29;352(6285):aad3873. doi: 10.1126/science.aad3873. Epub 2016 Mar 10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Neurobiology Division, Medical Research Council (MRC) Laboratory of Molecular Biology, Cambridge, UK. ; Structural Studies Division, MRC Laboratory of Molecular Biology, Cambridge, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26966189" target="_blank"〉PubMed〈/a〉
    Keywords: Brain/metabolism ; Cryoelectron Microscopy ; Crystallography, X-Ray ; HEK293 Cells ; Humans ; Ligands ; Models, Molecular ; *Protein Multimerization ; Protein Structure, Tertiary ; Receptors, AMPA/*chemistry/ultrastructure
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 2
    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
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 3
    Publication Date: 2016-01-30
    Description: p97 is a hexameric AAA+ adenosine triphosphatase (ATPase) that is an attractive target for cancer drug development. We report cryo-electron microscopy (cryo-EM) structures for adenosine diphosphate (ADP)-bound, full-length, hexameric wild-type p97 in the presence and absence of an allosteric inhibitor at resolutions of 2.3 and 2.4 angstroms, respectively. We also report cryo-EM structures (at resolutions of ~3.3, 3.2, and 3.3 angstroms, respectively) for three distinct, coexisting functional states of p97 with occupancies of zero, one, or two molecules of adenosine 5'-O-(3-thiotriphosphate) (ATPgammaS) per protomer. A large corkscrew-like change in molecular architecture, coupled with upward displacement of the N-terminal domain, is observed only when ATPgammaS is bound to both the D1 and D2 domains of the protomer. These cryo-EM structures establish the sequence of nucleotide-driven structural changes in p97 at atomic resolution. They also enable elucidation of the binding mode of an allosteric small-molecule inhibitor to p97 and illustrate how inhibitor binding at the interface between the D1 and D2 domains prevents propagation of the conformational changes necessary for p97 function.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Banerjee, Soojay -- Bartesaghi, Alberto -- Merk, Alan -- Rao, Prashant -- Bulfer, Stacie L -- Yan, Yongzhao -- Green, Neal -- Mroczkowski, Barbara -- Neitz, R Jeffrey -- Wipf, Peter -- Falconieri, Veronica -- Deshaies, Raymond J -- Milne, Jacqueline L S -- Huryn, Donna -- Arkin, Michelle -- Subramaniam, Sriram -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2016 Feb 19;351(6275):871-5. doi: 10.1126/science.aad7974. Epub 2016 Jan 28.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Cell Biology, National Cancer Institute, Bethesda, MD 20892, USA. ; Small Molecule Discovery Center, Pharmaceutical Chemistry, School of Pharmacy, University of California, San Francisco, CA 94143, USA. ; University of Pittsburgh Chemical Diversity Center, University of Pittsburgh, Pittsburgh, PA 15260, USA. ; Leidos Biomedical Research Inc., Frederick, MD 21702, USA. ; Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD 20892, USA. ; Division of Biology and Biological Engineering and Howard Hughes Medical Institute, California Institute of Technology, Pasadena, CA 91107, USA. ; Laboratory of Cell Biology, National Cancer Institute, Bethesda, MD 20892, USA. ss1@nih.gov.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26822609" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Diphosphate/chemistry ; Adenosine Triphosphatases/*antagonists & inhibitors/*chemistry ; Adenosine Triphosphate/analogs & derivatives/chemistry ; Allosteric Regulation ; Binding Sites ; Cryoelectron Microscopy ; Enzyme Inhibitors ; Humans ; Models, Molecular ; Nuclear Proteins/*antagonists & inhibitors/*chemistry ; Protein Structure, Tertiary
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 4
    Publication Date: 2016-02-26
    Description: Hundreds of pathways for degradation converge at ubiquitin recognition by a proteasome. Here, we found that the five known proteasomal ubiquitin receptors in yeast are collectively nonessential for ubiquitin recognition and identified a sixth receptor, Rpn1. A site ( T1: ) in the Rpn1 toroid recognized ubiquitin and ubiquitin-like ( UBL: ) domains of substrate shuttling factors. T1 structures with monoubiquitin or lysine 48 diubiquitin show three neighboring outer helices engaging two ubiquitins. T1 contributes a distinct substrate-binding pathway with preference for lysine 48-linked chains. Proximal to T1 within the Rpn1 toroid is a second UBL-binding site ( T2: ) that assists in ubiquitin chain disassembly, by binding the UBL of deubiquitinating enzyme Ubp6. Thus, a two-site recognition domain intrinsic to the proteasome uses distinct ubiquitin-fold ligands to assemble substrates, shuttling factors, and a deubiquitinating enzyme.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shi, Yuan -- Chen, Xiang -- Elsasser, Suzanne -- Stocks, Bradley B -- Tian, Geng -- Lee, Byung-Hoon -- Shi, Yanhong -- Zhang, Naixia -- de Poot, Stefanie A H -- Tuebing, Fabian -- Sun, Shuangwu -- Vannoy, Jacob -- Tarasov, Sergey G -- Engen, John R -- Finley, Daniel -- Walters, Kylie J -- New York, N.Y. -- Science. 2016 Feb 19;351(6275). pii: aad9421. doi: 10.1126/science.aad9421.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA. ; Protein Processing Section, Structural Biophysics Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA. ; Department of Chemistry and Chemical Biology, Northeastern University, Boston, MA 02115, USA. ; Protein Processing Section, Structural Biophysics Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA. Department of Analytical Chemistry, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, P. R. China. ; Department of Analytical Chemistry, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, P. R. China. ; Protein Processing Section, Structural Biophysics Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA. Linganore High School, Frederick, MD 21701, USA. ; Biophysics Resource, Structural Biophysics Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA. ; Department of Chemistry and Chemical Biology, Northeastern University, Boston, MA 02115, USA. j.engen@neu.edu kylie.walters@nih.gov daniel_finley@hms.harvard.edu. ; Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA. j.engen@neu.edu kylie.walters@nih.gov daniel_finley@hms.harvard.edu. ; Protein Processing Section, Structural Biophysics Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA. j.engen@neu.edu kylie.walters@nih.gov daniel_finley@hms.harvard.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26912900" target="_blank"〉PubMed〈/a〉
    Keywords: DNA-Binding Proteins/metabolism ; Endopeptidases/metabolism ; Metabolic Networks and Pathways ; Models, Molecular ; Mutation ; Proteasome Endopeptidase Complex/chemistry/genetics/*metabolism ; Saccharomyces cerevisiae/*metabolism ; Saccharomyces cerevisiae Proteins/*chemistry/genetics/*metabolism ; Ubiquitin-Specific Proteases/metabolism ; Ubiquitination
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 5
    Publication Date: 2016-03-12
    Description: Type IVa pili are filamentous cell surface structures observed in many bacteria. They pull cells forward by extending, adhering to surfaces, and then retracting. We used cryo-electron tomography of intact Myxococcus xanthus cells to visualize type IVa pili and the protein machine that assembles and retracts them (the type IVa pilus machine, or T4PM) in situ, in both the piliated and nonpiliated states, at a resolution of 3 to 4 nanometers. We found that T4PM comprises an outer membrane pore, four interconnected ring structures in the periplasm and cytoplasm, a cytoplasmic disc and dome, and a periplasmic stem. By systematically imaging mutants lacking defined T4PM proteins or with individual proteins fused to tags, we mapped the locations of all 10 T4PM core components and the minor pilins, thereby providing insights into pilus assembly, structure, and function.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chang, Yi-Wei -- Rettberg, Lee A -- Treuner-Lange, Anke -- Iwasa, Janet -- Sogaard-Andersen, Lotte -- Jensen, Grant J -- R01 GM094800B/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2016 Mar 11;351(6278):aad2001. doi: 10.1126/science.aad2001. Epub 2016 Mar 10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉California Institute of Technology, Pasadena, CA 91125, USA. Howard Hughes Medical Institute, Pasadena, CA 91125, USA. ; Howard Hughes Medical Institute, Pasadena, CA 91125, USA. ; Max Planck Institute for Terrestrial Microbiology, 35043 Marburg, Germany. ; University of Utah, Salt Lake City, UT 84112, USA. ; California Institute of Technology, Pasadena, CA 91125, USA. Howard Hughes Medical Institute, Pasadena, CA 91125, USA. jensen@caltech.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26965631" target="_blank"〉PubMed〈/a〉
    Keywords: Bacterial Adhesion ; Cryoelectron Microscopy ; Fimbriae, Bacterial/genetics/*ultrastructure ; Microscopy, Electron, Transmission ; Models, Molecular ; Mutation ; Myxococcus xanthus/genetics/physiology/*ultrastructure
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 6
    Publication Date: 2016-04-16
    Description: Nuclear pore complexes (NPCs) are 110-megadalton assemblies that mediate nucleocytoplasmic transport. NPCs are built from multiple copies of ~30 different nucleoporins, and understanding how these nucleoporins assemble into the NPC scaffold imposes a formidable challenge. Recently, it has been shown how the Y complex, a prominent NPC module, forms the outer rings of the nuclear pore. However, the organization of the inner ring has remained unknown until now. We used molecular modeling combined with cross-linking mass spectrometry and cryo-electron tomography to obtain a composite structure of the inner ring. This architectural map explains the vast majority of the electron density of the scaffold. We conclude that despite obvious differences in morphology and composition, the higher-order structure of the inner and outer rings is unexpectedly similar.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kosinski, Jan -- Mosalaganti, Shyamal -- von Appen, Alexander -- Teimer, Roman -- DiGuilio, Amanda L -- Wan, William -- Bui, Khanh Huy -- Hagen, Wim J H -- Briggs, John A G -- Glavy, Joseph S -- Hurt, Ed -- Beck, Martin -- 1R21AG047433-01/AG/NIA NIH HHS/ -- R21 AG047433/AG/NIA NIH HHS/ -- New York, N.Y. -- Science. 2016 Apr 15;352(6283):363-5. doi: 10.1126/science.aaf0643.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Structural and Computational Biology Unit, European Molecular Biology Laboratory (EMBL), Heidelberg, Germany. ; Biochemistry Center of Heidelberg University, Im Neuenheimer Feld 328, D-69120 Heidelberg, Germany. ; Department of Chemistry, Chemical Biology and Biomedical Engineering, Stevens Institute of Technology, 507 River Street, Hoboken, NJ 07030, USA. ; Department of Anatomy and Cell Biology, McGill University, Montreal, Quebec, Canada. ; Structural and Computational Biology Unit, European Molecular Biology Laboratory (EMBL), Heidelberg, Germany. Cell Biology and Biophysics Unit, EMBL, Heidelberg, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27081072" target="_blank"〉PubMed〈/a〉
    Keywords: Active Transport, Cell Nucleus ; Cryoelectron Microscopy ; Electron Microscope Tomography ; HeLa Cells ; Humans ; Mass Spectrometry ; Models, Molecular ; Nuclear Matrix/metabolism/ultrastructure ; Nuclear Pore/*metabolism/*ultrastructure ; Nuclear Pore Complex Proteins/chemistry/genetics/*metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 7
    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
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 8
    Publication Date: 2015-01-31
    Description: Coordinated replication and expression of the mitochondrial genome is critical for metabolically active cells during various stages of development. However, it is not known whether replication and transcription can occur simultaneously without interfering with each other and whether mitochondrial DNA copy number can be regulated by the transcription machinery. We found that interaction of human transcription elongation factor TEFM with mitochondrial RNA polymerase and nascent transcript prevents the generation of replication primers and increases transcription processivity and thereby serves as a molecular switch between replication and transcription, which appear to be mutually exclusive processes in mitochondria. TEFM may allow mitochondria to increase transcription rates and, as a consequence, respiration and adenosine triphosphate production without the need to replicate mitochondrial DNA, as has been observed during spermatogenesis and the early stages of embryogenesis.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4677687/" 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/PMC4677687/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Agaronyan, Karen -- Morozov, Yaroslav I -- Anikin, Michael -- Temiakov, Dmitry -- R01 GM104231/GM/NIGMS NIH HHS/ -- R01GM104231/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2015 Jan 30;347(6221):548-51. doi: 10.1126/science.aaa0986.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cell Biology, School of Osteopathic Medicine, Rowan University, 2 Medical Center Drive, Stratford, NJ 08084, USA. ; Department of Cell Biology, School of Osteopathic Medicine, Rowan University, 2 Medical Center Drive, Stratford, NJ 08084, USA. temiakdm@rowan.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25635099" target="_blank"〉PubMed〈/a〉
    Keywords: *DNA Replication ; DNA, Mitochondrial/*genetics/*metabolism ; DNA-Directed RNA Polymerases/chemistry/*metabolism ; G-Quadruplexes ; Genome, Mitochondrial ; Humans ; Mitochondria/genetics/metabolism ; Mitochondrial Proteins/chemistry/*metabolism ; Models, Genetic ; Models, Molecular ; RNA/chemistry/*metabolism ; Transcription Factors/*metabolism ; Transcription Termination, Genetic ; *Transcription, Genetic
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 9
    Publication Date: 2015-08-22
    Description: Splicing of precursor messenger RNA (pre-mRNA) in yeast is executed by the spliceosome, which consists of five small nuclear ribonucleoproteins (snRNPs), NTC (nineteen complex), NTC-related proteins (NTR), and a number of associated enzymes and cofactors. Here, we report the three-dimensional structure of a Schizosaccharomyces pombe spliceosome at 3.6-angstrom resolution, revealed by means of single-particle cryogenic electron microscopy. This spliceosome contains U2 and U5 snRNPs, NTC, NTR, U6 small nuclear RNA, and an RNA intron lariat. The atomic model includes 10,574 amino acids from 37 proteins and four RNA molecules, with a combined molecular mass of approximately 1.3 megadaltons. Spp42 (Prp8 in Saccharomyces cerevisiae), the key protein component of the U5 snRNP, forms a central scaffold and anchors the catalytic center. Both the morphology and the placement of protein components appear to have evolved to facilitate the dynamic process of pre-mRNA splicing. Our near-atomic-resolution structure of a central spliceosome provides a molecular framework for mechanistic understanding of pre-mRNA splicing.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yan, Chuangye -- Hang, Jing -- Wan, Ruixue -- Huang, Min -- Wong, Catherine C L -- Shi, Yigong -- New York, N.Y. -- Science. 2015 Sep 11;349(6253):1182-91. doi: 10.1126/science.aac7629. 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. ; 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/26292707" target="_blank"〉PubMed〈/a〉
    Keywords: Catalytic Domain ; Cryoelectron Microscopy ; Models, Molecular ; Protein Structure, Secondary ; RNA, Small Nuclear/chemistry ; Repressor Proteins/chemistry ; Ribonucleoprotein, U5 Small Nuclear/chemistry ; Schizosaccharomyces/*ultrastructure ; Schizosaccharomyces pombe Proteins/chemistry ; Spliceosomes/*chemistry/*ultrastructure
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 10
    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
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 11
    Publication Date: 2015-12-19
    Description: Voltage-gated sodium (Nav) channels propagate action potentials in excitable cells. Accordingly, Nav channels are therapeutic targets for many cardiovascular and neurological disorders. Selective inhibitors have been challenging to design because the nine mammalian Nav channel isoforms share high sequence identity and remain recalcitrant to high-resolution structural studies. Targeting the human Nav1.7 channel involved in pain perception, we present a protein-engineering strategy that has allowed us to determine crystal structures of a novel receptor site in complex with isoform-selective antagonists. GX-936 and related inhibitors bind to the activated state of voltage-sensor domain IV (VSD4), where their anionic aryl sulfonamide warhead engages the fourth arginine gating charge on the S4 helix. By opposing VSD4 deactivation, these compounds inhibit Nav1.7 through a voltage-sensor trapping mechanism, likely by stabilizing inactivated states of the channel. Residues from the S2 and S3 helices are key determinants of isoform selectivity, and bound phospholipids implicate the membrane as a modulator of channel function and pharmacology. Our results help to elucidate the molecular basis of voltage sensing and establish structural blueprints to design selective Nav channel antagonists.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ahuja, Shivani -- Mukund, Susmith -- Deng, Lunbin -- Khakh, Kuldip -- Chang, Elaine -- Ho, Hoangdung -- Shriver, Stephanie -- Young, Clint -- Lin, Sophia -- Johnson, J P Jr -- Wu, Ping -- Li, Jun -- Coons, Mary -- Tam, Christine -- Brillantes, Bobby -- Sampang, Honorio -- Mortara, Kyle -- Bowman, Krista K -- Clark, Kevin R -- Estevez, Alberto -- Xie, Zhiwei -- Verschoof, Henry -- Grimwood, Michael -- Dehnhardt, Christoph -- Andrez, Jean-Christophe -- Focken, Thilo -- Sutherlin, Daniel P -- Safina, Brian S -- Starovasnik, Melissa A -- Ortwine, Daniel F -- Franke, Yvonne -- Cohen, Charles J -- Hackos, David H -- Koth, Christopher M -- Payandeh, Jian -- New York, N.Y. -- Science. 2015 Dec 18;350(6267):aac5464. doi: 10.1126/science.aac5464.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Structural Biology, Genentech Inc., South San Francisco, CA 94080, USA. ; Department of Neuroscience, Genentech Inc., South San Francisco, CA 94080, USA. ; Department of Biology, Xenon Pharmaceuticals Inc., Burnaby, British Columbia, V5G 4W8, Canada. ; Department of Discovery Chemistry, Genentech Inc., South San Francisco, CA 94080, USA. ; Department of Biochemical and Cellular Pharmacology, Genentech Inc., South San Francisco, CA 94080, USA. ; Department of Chemistry, Xenon Pharmaceuticals Inc., Burnaby, British Columbia, V5G 4W8, Canada. ; Department of Neuroscience, Genentech Inc., South San Francisco, CA 94080, USA. hackos.david@gene.com koth.christopher@gene.com payandeh.jian@gene.com. ; Department of Structural Biology, Genentech Inc., South San Francisco, CA 94080, USA. hackos.david@gene.com koth.christopher@gene.com payandeh.jian@gene.com.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26680203" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Cell Membrane/chemistry ; Crystallization/methods ; Crystallography, X-Ray ; DNA Mutational Analysis ; Humans ; Models, Molecular ; Molecular Sequence Data ; NAV1.7 Voltage-Gated Sodium Channel/*chemistry/genetics ; Pain Perception/drug effects ; Protein Engineering ; Protein Isoforms/antagonists & inhibitors/chemistry ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Sodium Channel Blockers/*chemistry/*pharmacology ; Sulfonamides/*chemistry/*pharmacology ; Thiadiazoles/*chemistry/*pharmacology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 12
    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
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 13
    Publication Date: 2014-12-17
    Description: Iron sequestration provides an innate defense, termed nutritional immunity, leading pathogens to scavenge iron from hosts. Although the molecular basis of this battle for iron is established, its potential as a force for evolution at host-pathogen interfaces is unknown. We show that the iron transport protein transferrin is engaged in ancient and ongoing evolutionary conflicts with TbpA, a transferrin surface receptor from bacteria. Single substitutions in transferrin at rapidly evolving sites reverse TbpA binding, providing a mechanism to counteract bacterial iron piracy among great apes. Furthermore, the C2 transferrin polymorphism in humans evades TbpA variants from Haemophilus influenzae, revealing a functional basis for standing genetic variation. These findings identify a central role for nutritional immunity in the persistent evolutionary conflicts between primates and bacterial pathogens.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4455941/" 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/PMC4455941/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Barber, Matthew F -- Elde, Nels C -- 1F32GM108288/GM/NIGMS NIH HHS/ -- GM090042/GM/NIGMS NIH HHS/ -- R00 GM090042/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2014 Dec 12;346(6215):1362-6. doi: 10.1126/science.1259329.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Human Genetics, University of Utah School of Medicine, Salt Lake City, UT 84112, USA. ; Department of Human Genetics, University of Utah School of Medicine, Salt Lake City, UT 84112, USA. nelde@genetics.utah.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25504720" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Amino Acid Substitution ; Animals ; Evolution, Molecular ; Haemophilus influenzae/*metabolism ; Haplorhini/*genetics/immunology/*metabolism ; Humans ; Immunity, Innate ; Models, Molecular ; Molecular Sequence Data ; Neisseria/*metabolism ; Neisseria gonorrhoeae/metabolism ; Neisseria meningitidis/metabolism ; Phylogeny ; Polymorphism, Genetic ; Protein Binding ; Selection, Genetic ; Transferrin/chemistry/*genetics/*metabolism ; Transferrin-Binding Protein A/chemistry/*genetics/*metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 14
    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
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 15
    Publication Date: 2014-04-20
    Description: Cytoplasmic plant immune receptors recognize specific pathogen effector proteins and initiate effector-triggered immunity. In Arabidopsis, the immune receptors RPS4 and RRS1 are both required to activate defense to three different pathogens. We show that RPS4 and RRS1 physically associate. Crystal structures of the N-terminal Toll-interleukin-1 receptor/resistance (TIR) domains of RPS4 and RRS1, individually and as a heterodimeric complex (respectively at 2.05, 1.75, and 2.65 angstrom resolution), reveal a conserved TIR/TIR interaction interface. We show that TIR domain heterodimerization is required to form a functional RRS1/RPS4 effector recognition complex. The RPS4 TIR domain activates effector-independent defense, which is inhibited by the RRS1 TIR domain through the heterodimerization interface. Thus, RPS4 and RRS1 function as a receptor complex in which the two components play distinct roles in recognition and signaling.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Williams, Simon J -- Sohn, Kee Hoon -- Wan, Li -- Bernoux, Maud -- Sarris, Panagiotis F -- Segonzac, Cecile -- Ve, Thomas -- Ma, Yan -- Saucet, Simon B -- Ericsson, Daniel J -- Casey, Lachlan W -- Lonhienne, Thierry -- Winzor, Donald J -- Zhang, Xiaoxiao -- Coerdt, Anne -- Parker, Jane E -- Dodds, Peter N -- Kobe, Bostjan -- Jones, Jonathan D G -- New York, N.Y. -- Science. 2014 Apr 18;344(6181):299-303. doi: 10.1126/science.1247357.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉School of Chemistry and Molecular Biosciences and Australian Infectious Diseases Research Centre, University of Queensland, Brisbane, QLD 4072, Australia.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24744375" target="_blank"〉PubMed〈/a〉
    Keywords: Agrobacterium/physiology ; Amino Acid Motifs ; Arabidopsis/chemistry/*immunology/microbiology ; Arabidopsis Proteins/*chemistry/genetics/metabolism ; Bacterial Proteins/immunology/metabolism ; Cell Death ; Crystallography, X-Ray ; Immunity, Innate ; Models, Molecular ; Mutation ; Plant Diseases/immunology/microbiology ; Plant Leaves/microbiology ; Plant Proteins/*chemistry/genetics/metabolism ; Plants, Genetically Modified ; Protein Interaction Domains and Motifs ; Protein Multimerization ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Receptors, Immunologic/*chemistry/genetics/metabolism ; Signal Transduction ; Tobacco/genetics/immunology/metabolism/microbiology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 16
    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
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 17
    Publication Date: 2014-12-17
    Description: Some HIV-infected individuals develop broadly neutralizing antibodies (bNAbs), whereas most develop antibodies that neutralize only a narrow range of viruses (nNAbs). bNAbs, but not nNAbs, protect animals from experimental infection and are likely a key component of an effective vaccine. nNAbs and bNAbs target the same regions of the viral envelope glycoprotein (Env), but for reasons that remain unclear only nNAbs are elicited by Env immunization. We show that in contrast to germline-reverted (gl) bNAbs, glnNAbs recognized diverse recombinant Envs. Moreover, owing to binding affinity differences, nNAb B cell progenitors had an advantage in becoming activated and internalizing Env compared with bNAb B cell progenitors. We then identified an Env modification strategy that minimized the activation of nNAb B cells targeting epitopes that overlap those of bNAbs.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4290850/" 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/PMC4290850/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉McGuire, Andrew T -- Dreyer, Anita M -- Carbonetti, Sara -- Lippy, Adriana -- Glenn, Jolene -- Scheid, Johannes F -- Mouquet, Hugo -- Stamatatos, Leonidas -- P01 AI094419/AI/NIAID NIH HHS/ -- P01 AI094419-01/AI/NIAID NIH HHS/ -- U19 19AI109632-01/AI/NIAID NIH HHS/ -- U19 AI109632/AI/NIAID NIH HHS/ -- Canadian Institutes of Health Research/Canada -- New York, N.Y. -- Science. 2014 Dec 12;346(6215):1380-3. doi: 10.1126/science.1259206.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Seattle Biomedical Research Institute, Seattle, WA 98109, USA. ; Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA. ; Laboratory of Humoral Response to Pathogens, Department of Immunology, Institut Pasteur and CNRS-URA 1961, 75015 Paris, France. ; Seattle Biomedical Research Institute, Seattle, WA 98109, USA. Department of Global Health, University of Washington, Seattle, WA 98109, USA. lstamata@fhcrc.org.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25504724" target="_blank"〉PubMed〈/a〉
    Keywords: AIDS Vaccines/immunology ; Antibodies, Neutralizing/*immunology ; Antibody Affinity ; B-Lymphocytes/immunology ; Binding, Competitive ; Epitopes/immunology ; HIV Antibodies/genetics/*immunology ; HIV-1/*immunology ; Humans ; Lymphocyte Activation ; Models, Molecular ; Receptors, Antigen, B-Cell/genetics/immunology ; Recombinant Proteins/immunology ; env Gene Products, Human Immunodeficiency Virus/chemistry/genetics/*immunology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 18
    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
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 19
    Publication Date: 2014-12-06
    Description: The prevention of fertilization through self-pollination (or pollination by a close relative) in the Brassicaceae plant family is determined by the genotype of the plant at the self-incompatibility locus (S locus). The many alleles at this locus exhibit a dominance hierarchy that determines which of the two allelic specificities of a heterozygous genotype is expressed at the phenotypic level. Here, we uncover the evolution of how at least 17 small RNA (sRNA)-producing loci and their multiple target sites collectively control the dominance hierarchy among alleles within the gene controlling the pollen S-locus phenotype in a self-incompatible Arabidopsis species. Selection has created a dynamic repertoire of sRNA-target interactions by jointly acting on sRNA genes and their target sites, which has resulted in a complex system of regulation among alleles.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Durand, Eleonore -- Meheust, Raphael -- Soucaze, Marion -- Goubet, Pauline M -- Gallina, Sophie -- Poux, Celine -- Fobis-Loisy, Isabelle -- Guillon, Eline -- Gaude, Thierry -- Sarazin, Alexis -- Figeac, Martin -- Prat, Elisa -- Marande, William -- Berges, Helene -- Vekemans, Xavier -- Billiard, Sylvain -- Castric, Vincent -- New York, N.Y. -- Science. 2014 Dec 5;346(6214):1200-5. doi: 10.1126/science.1259442.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratoire Genetique et Evolution des Populations Vegetales, CNRS UMR 8198, Universite Lille 1, F-59655 Villeneuve d'Ascq cedex, France. ; Reproduction et Developpement des Plantes, Institut Federatif de Recherche 128, Centre National de la Recherche Scientifique, Institut National de la Recherche Agronomique, Universite Claude Bernard Lyon I, Ecole Normale Superieure de Lyon, F-69364 Lyon, Cedex 07, France. ; Department of Biology, Swiss Federal Institute of Technology Zurich, CH-8093 Zurich, Switzerland. ; UDSL Universite Lille 2 Droit et Sante, and Plate-forme de genomique fonctionnelle et structurale IFR-114, F-59000 Lille, France. ; Centre National des Ressources Genomiques Vegetales, INRA UPR 1258, Castanet-Tolosan, France. ; Laboratoire Genetique et Evolution des Populations Vegetales, CNRS UMR 8198, Universite Lille 1, F-59655 Villeneuve d'Ascq cedex, France. vincent.castric@univ-lille1.fr.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25477454" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Arabidopsis/*genetics ; *Biological Evolution ; *Gene Expression Regulation, Plant ; *Gene Regulatory Networks ; *Genes, Dominant ; *Genes, Recessive ; Genetic Loci ; Models, Molecular ; Phylogeny ; Pollination ; RNA, Small Untranslated/classification/*genetics ; Selection, Genetic
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 20
    Publication Date: 2014-08-16
    Description: In prokaryotes, RNA derived from type I and type III CRISPR loci direct large ribonucleoprotein complexes to destroy invading bacteriophage and plasmids. In Escherichia coli, this 405-kilodalton complex is called Cascade. We report the crystal structure of Cascade bound to a single-stranded DNA (ssDNA) target at a resolution of 3.03 angstroms. The structure reveals that the CRISPR RNA and target strands do not form a double helix but instead adopt an underwound ribbon-like structure. This noncanonical structure is facilitated by rotation of every sixth nucleotide out of the RNA-DNA hybrid and is stabilized by the highly interlocked organization of protein subunits. These studies provide insight into both the assembly and the activity of this complex and suggest a mechanism to enforce fidelity of target binding.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4427192/" 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/PMC4427192/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mulepati, Sabin -- Heroux, Annie -- Bailey, Scott -- GM097330/GM/NIGMS NIH HHS/ -- P41GM103393/GM/NIGMS NIH HHS/ -- P41GM103473/GM/NIGMS NIH HHS/ -- P41RR012408/RR/NCRR NIH HHS/ -- R01 GM097330/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2014 Sep 19;345(6203):1479-84. doi: 10.1126/science.1256996. Epub 2014 Aug 14.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA. ; Photon Sciences Directorate, Brookhaven National Laboratory, Upton, NY 11973, USA. ; Department of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA. scott.bailey@jhu.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25123481" target="_blank"〉PubMed〈/a〉
    Keywords: CRISPR-Associated Proteins/*chemistry ; *CRISPR-Cas Systems ; *Clustered Regularly Interspaced Short Palindromic Repeats ; Crystallography, X-Ray ; DNA Helicases/chemistry ; DNA, Single-Stranded/*chemistry ; Escherichia coli/*genetics ; Escherichia coli Proteins/*chemistry ; Models, Molecular ; RNA, Bacterial/*chemistry
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 21
    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
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 22
    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
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 23
    Publication Date: 2014-05-17
    Description: Signaling from JAK (Janus kinase) protein kinases to STAT (signal transducers and activators of transcription) transcription factors is key to many aspects of biology and medicine, yet the mechanism by which cytokine receptors initiate signaling is enigmatic. We present a complete mechanistic model for activation of receptor-bound JAK2, based on an archetypal cytokine receptor, the growth hormone receptor. For this, we used fluorescence resonance energy transfer to monitor positioning of the JAK2 binding motif in the receptor dimer, substitution of the receptor extracellular domains with Jun zippers to control the position of its transmembrane (TM) helices, atomistic modeling of TM helix movements, and docking of the crystal structures of the JAK2 kinase and its inhibitory pseudokinase domain with an opposing kinase-pseudokinase domain pair. Activation of the receptor dimer induced a separation of its JAK2 binding motifs, driven by a ligand-induced transition from a parallel TM helix pair to a left-handed crossover arrangement. This separation leads to removal of the pseudokinase domain from the kinase domain of the partner JAK2 and pairing of the two kinase domains, facilitating trans-activation. This model may well generalize to other class I cytokine receptors.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Brooks, Andrew J -- Dai, Wei -- O'Mara, Megan L -- Abankwa, Daniel -- Chhabra, Yash -- Pelekanos, Rebecca A -- Gardon, Olivier -- Tunny, Kathryn A -- Blucher, Kristopher M -- Morton, Craig J -- Parker, Michael W -- Sierecki, Emma -- Gambin, Yann -- Gomez, Guillermo A -- Alexandrov, Kirill -- Wilson, Ian A -- Doxastakis, Manolis -- Mark, Alan E -- Waters, Michael J -- New York, N.Y. -- Science. 2014 May 16;344(6185):1249783. doi: 10.1126/science.1249783.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The University of Queensland, Institute for Molecular Bioscience (IMB), St Lucia, Queensland 4072, Australia. m.waters@uq.edu.au a.brooks@uq.edu.au. ; Department of Chemical and Biomolecular Engineering, University of Houston, Houston, TX 77004, USA. ; The University of Queensland, School of Chemistry and Molecular Biosciences, St Lucia, Queensland 4072, Australia. ; The University of Queensland, Institute for Molecular Bioscience (IMB), St Lucia, Queensland 4072, Australia. ; Biota Structural Biology Laboratory and Australian Cancer Research Foundation (ACRF) Rational Drug Discovery Centre, St Vincent's Institute of Medical Research, Fitzroy, Victoria 3065, Australia. ; Biota Structural Biology Laboratory and Australian Cancer Research Foundation (ACRF) Rational Drug Discovery Centre, St Vincent's Institute of Medical Research, Fitzroy, Victoria 3065, Australia. Department of Biochemistry and Molecular Biology and Bio21 Institute, University of Melbourne, Parkville, Victoria 3052, Australia. ; Scripps Research Institute, La Jolla, CA 92037, USA. ; The University of Queensland, Institute for Molecular Bioscience (IMB), St Lucia, Queensland 4072, Australia. The University of Queensland, School of Chemistry and Molecular Biosciences, St Lucia, Queensland 4072, Australia.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24833397" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Motifs ; Amino Acid Sequence ; Cysteine/chemistry ; Enzyme Activation ; HEK293 Cells ; Humans ; Janus Kinase 2/antagonists & inhibitors/chemistry/*metabolism ; Models, Molecular ; Molecular Sequence Data ; Mutation ; Protein Multimerization ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Receptors, Somatotropin/chemistry/genetics/*metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 24
    facet.materialart.
    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-11-02
    Description: MicroRNAs (miRNAs) control expression of thousands of genes in plants and animals. miRNAs function by guiding Argonaute proteins to complementary sites in messenger RNAs (mRNAs) targeted for repression. We determined crystal structures of human Argonaute-2 (Ago2) bound to a defined guide RNA with and without target RNAs representing miRNA recognition sites. These structures suggest a stepwise mechanism, in which Ago2 primarily exposes guide nucleotides (nt) 2 to 5 for initial target pairing. Pairing to nt 2 to 5 promotes conformational changes that expose nt 2 to 8 and 13 to 16 for further target recognition. Interactions with the guide-target minor groove allow Ago2 to interrogate target RNAs in a sequence-independent manner, whereas an adenosine binding-pocket opposite guide nt 1 further facilitates target recognition. Spurious slicing of miRNA targets is avoided through an inhibitory coordination of one catalytic magnesium ion. These results explain the conserved nucleotide-pairing patterns in animal miRNA target sites first observed over two decades ago.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4313529/" 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/PMC4313529/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schirle, Nicole T -- Sheu-Gruttadauria, Jessica -- MacRae, Ian J -- P41 GM103403/GM/NIGMS NIH HHS/ -- R01 GM104475/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2014 Oct 31;346(6209):608-13. doi: 10.1126/science.1258040.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Integrative Structural and Computational Biology, 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. macrae@scripps.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25359968" target="_blank"〉PubMed〈/a〉
    Keywords: Argonaute Proteins/*chemistry/genetics ; Base Sequence ; Catalytic Domain ; Conserved Sequence ; Crystallography, X-Ray ; *Gene Expression Regulation ; Humans ; Magnesium/chemistry ; MicroRNAs/*chemistry/genetics ; Models, Molecular ; Nucleic Acid Conformation ; Protein Structure, Secondary ; RNA, Guide/*chemistry/genetics
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 25
    Publication Date: 2014-06-07
    Description: Calcium homeostasis balances passive calcium leak and active calcium uptake. Human Bax inhibitor-1 (hBI-1) is an antiapoptotic protein that mediates a calcium leak and is representative of a highly conserved and widely distributed family, the transmembrane Bax inhibitor motif (TMBIM) proteins. Here, we present crystal structures of a bacterial homolog and characterize its calcium leak activity. The structure has a seven-transmembrane-helix fold that features two triple-helix sandwiches wrapped around a central C-terminal helix. Structures obtained in closed and open conformations are reversibly interconvertible by change of pH. A hydrogen-bonded, pKa (where Ka is the acid dissociation constant)-perturbed pair of conserved aspartate residues explains the pH dependence of this transition, and biochemical studies show that pH regulates calcium influx in proteoliposomes. Homology models for hBI-1 provide insights into TMBIM-mediated calcium leak and cytoprotective activity.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4119810/" 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/PMC4119810/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chang, Yanqi -- Bruni, Renato -- Kloss, Brian -- Assur, Zahra -- Kloppmann, Edda -- Rost, Burkhard -- Hendrickson, Wayne A -- Liu, Qun -- GM095315/GM/NIGMS NIH HHS/ -- GM107462/GM/NIGMS NIH HHS/ -- R01 GM107462/GM/NIGMS NIH HHS/ -- U54 GM095315/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2014 Jun 6;344(6188):1131-5. doi: 10.1126/science.1252043.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉New York Consortium on Membrane Protein Structure, New York Structural Biology Center, New York, NY 10027, USA. ; Department of Physiology and Cellular Biophysics, Columbia University, New York, NY 10032, USA. ; New York Consortium on Membrane Protein Structure, New York Structural Biology Center, New York, NY 10027, USA. Department of Bioinformatics and Computational Biology, Fakultat fur Informatik, Technische Universitat Munchen, Garching, Germany. ; New York Consortium on Membrane Protein Structure, New York Structural Biology Center, New York, NY 10027, USA. Department of Physiology and Cellular Biophysics, Columbia University, New York, NY 10032, USA. New York Structural Biology Center, National Synchrotron Light Source (NSLS) X4, Brookhaven National Laboratory, Upton, NY 11973, USA. Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA. ; New York Consortium on Membrane Protein Structure, New York Structural Biology Center, New York, NY 10027, USA. New York Structural Biology Center, National Synchrotron Light Source (NSLS) X4, Brookhaven National Laboratory, Upton, NY 11973, USA. qunliu@bnl.gov.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24904158" target="_blank"〉PubMed〈/a〉
    Keywords: Bacillus subtilis/*metabolism ; Bacterial Proteins/*chemistry/metabolism ; Calcium/*metabolism ; Cell Membrane/*metabolism ; Crystallography, X-Ray ; Humans ; Hydrogen-Ion Concentration ; Membrane Proteins/*chemistry/metabolism ; Models, Molecular ; Protein Structure, Secondary
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 26
    Publication Date: 2014-04-20
    Description: Flaviviruses are emerging human pathogens and worldwide health threats. During infection, pathogenic subgenomic flaviviral RNAs (sfRNAs) are produced by resisting degradation by the 5'--〉3' host cell exonuclease Xrn1 through an unknown RNA structure-based mechanism. Here, we present the crystal structure of a complete Xrn1-resistant flaviviral RNA, which contains interwoven pseudoknots within a compact structure that depends on highly conserved nucleotides. The RNA's three-dimensional topology creates a ringlike conformation, with the 5' end of the resistant structure passing through the ring from one side of the fold to the other. Disruption of this structure prevents formation of sfRNA during flaviviral infection. Thus, sfRNA formation results from an RNA fold that interacts directly with Xrn1, presenting the enzyme with a structure that confounds its helicase activity.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4163914/" 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/PMC4163914/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chapman, Erich G -- Costantino, David A -- Rabe, Jennifer L -- Moon, Stephanie L -- Wilusz, Jeffrey -- Nix, Jay C -- Kieft, Jeffrey S -- P30 CA046934/CA/NCI NIH HHS/ -- P30CA046934/CA/NCI NIH HHS/ -- U54 AI-065357/AI/NIAID NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2014 Apr 18;344(6181):307-10. doi: 10.1126/science.1250897.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Molecular Genetics, School of Medicine, University of Colorado Denver, Aurora, CO 80045, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24744377" target="_blank"〉PubMed〈/a〉
    Keywords: Base Pairing ; Base Sequence ; Crystallography, X-Ray ; Encephalitis Virus, Murray Valley/*genetics/pathogenicity ; Exoribonucleases/metabolism ; Models, Molecular ; Molecular Sequence Data ; Mutation ; *Nucleic Acid Conformation ; RNA, Viral/*chemistry/genetics/metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 27
    Publication Date: 2014-10-18
    Description: Small molecules are useful tools for probing the biological function and therapeutic potential of individual proteins, but achieving selectivity is challenging when the target protein shares structural domains with other proteins. The Bromo and Extra-Terminal (BET) proteins have attracted interest because of their roles in transcriptional regulation, epigenetics, and cancer. The BET bromodomains (protein interaction modules that bind acetyl-lysine) have been targeted by potent small-molecule inhibitors, but these inhibitors lack selectivity for individual family members. We developed an ethyl derivative of an existing small-molecule inhibitor, I-BET/JQ1, and showed that it binds leucine/alanine mutant bromodomains with nanomolar affinity and achieves up to 540-fold selectivity relative to wild-type bromodomains. Cell culture studies showed that blockade of the first bromodomain alone is sufficient to displace a specific BET protein, Brd4, from chromatin. Expansion of this approach could help identify the individual roles of single BET proteins in human physiology and disease.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4458378/" 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/PMC4458378/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Baud, Matthias G J -- Lin-Shiao, Enrique -- Cardote, Teresa -- Tallant, Cynthia -- Pschibul, Annica -- Chan, Kwok-Ho -- Zengerle, Michael -- Garcia, Jordi R -- Kwan, Terence T-L -- Ferguson, Fleur M -- Ciulli, Alessio -- 097945/Z/11/Z/Wellcome Trust/United Kingdom -- 100476/Z/12/Z/Wellcome Trust/United Kingdom -- BB/G023123/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- BB/J001201/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- New York, N.Y. -- Science. 2014 Oct 31;346(6209):638-41. doi: 10.1126/science.1249830. Epub 2014 Oct 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee, James Black Centre, Dow Street, Dundee, DD1 5EH, UK. Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK. ; Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee, James Black Centre, Dow Street, Dundee, DD1 5EH, UK. ; Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK. ; Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee, James Black Centre, Dow Street, Dundee, DD1 5EH, UK. Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK. a.ciulli@dundee.ac.uk.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25323695" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Azepines/chemistry/pharmacology ; Cell Line, Tumor ; Chromatin/chemistry ; Crystallography, X-Ray ; Humans ; Leucine/genetics ; Models, Molecular ; Molecular Probes/*chemistry ; Mutation ; Nuclear Proteins/antagonists & inhibitors/*chemistry/genetics ; Protein Engineering/*methods ; Protein Structure, Tertiary ; Transcription Factors/antagonists & inhibitors/*chemistry/genetics ; Triazoles/chemistry/pharmacology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 28
    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
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 29
    Publication Date: 2013-03-23
    Description: Toll-like receptor 7 (TLR7) and TLR8 recognize single-stranded RNA and initiate innate immune responses. Several synthetic agonists of TLR7-TLR8 display novel therapeutic potential; however, the molecular basis for ligand recognition and activation of signaling by TLR7 or TLR8 is largely unknown. In this study, the crystal structures of unliganded and ligand-induced activated human TLR8 dimers were elucidated. Ligand recognition was mediated by a dimerization interface formed by two protomers. Upon ligand stimulation, the TLR8 dimer was reorganized such that the two C termini were brought into proximity. The loop between leucine-rich repeat 14 (LRR14) and LRR15 was cleaved; however, the N- and C-terminal halves remained associated and contributed to ligand recognition and dimerization. Thus, ligand binding induces reorganization of the TLR8 dimer, which enables downstream signaling processes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tanji, Hiromi -- Ohto, Umeharu -- Shibata, Takuma -- Miyake, Kensuke -- Shimizu, Toshiyuki -- New York, N.Y. -- Science. 2013 Mar 22;339(6126):1426-9. doi: 10.1126/science.1229159.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23520111" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Crystallography, X-Ray ; Humans ; Hydrogen Bonding ; Imidazoles/chemistry/*metabolism ; Ligands ; Models, Molecular ; Molecular Sequence Data ; Mutant Proteins/chemistry/metabolism ; Protein Binding ; Protein Conformation ; Protein Multimerization ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Quinolines/chemistry/*metabolism ; Signal Transduction ; Thiazoles/chemistry/*metabolism ; Toll-Like Receptor 8/*agonists/*chemistry/metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 30
    Publication Date: 2013-05-11
    Description: Mutations in the PARK2 (parkin) gene are responsible for an autosomal recessive form of Parkinson's disease. The parkin protein is a RING-in-between-RING E3 ubiquitin ligase that exhibits low basal activity. We describe the crystal structure of full-length rat parkin. The structure shows parkin in an autoinhibited state and provides insight into how it is activated. RING0 occludes the ubiquitin acceptor site Cys(431) in RING2, whereas a repressor element of parkin binds RING1 and blocks its E2-binding site. Mutations that disrupted these inhibitory interactions activated parkin both in vitro and in cells. Parkin is neuroprotective, and these findings may provide a structural and mechanistic framework for enhancing parkin activity.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Trempe, Jean-Francois -- Sauve, Veronique -- Grenier, Karl -- Seirafi, Marjan -- Tang, Matthew Y -- Menade, Marie -- Al-Abdul-Wahid, Sameer -- Krett, Jonathan -- Wong, Kathy -- Kozlov, Guennadi -- Nagar, Bhushan -- Fon, Edward A -- Gehring, Kalle -- MOP-14219/Canadian Institutes of Health Research/Canada -- MOP-62714/Canadian Institutes of Health Research/Canada -- New York, N.Y. -- Science. 2013 Jun 21;340(6139):1451-5. doi: 10.1126/science.1237908. Epub 2013 May 9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉McGill Parkinson Program, Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23661642" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Catalytic Domain ; Crystallography, X-Ray ; Enzyme Activation ; Hydrophobic and Hydrophilic Interactions ; Models, Molecular ; Molecular Sequence Data ; Mutation ; Parkinson Disease ; Parkinsonian Disorders ; Protein Binding ; Protein Conformation ; Protein Folding ; Protein Structure, Tertiary ; Rats ; Ubiquitin-Protein Ligases/*chemistry/genetics/*metabolism ; Ubiquitination ; Zinc Fingers
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 31
    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
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 32
    Publication Date: 2013-03-23
    Description: Engineering wireframe architectures and scaffolds of increasing complexity is one of the important challenges in nanotechnology. We present a design strategy to create gridiron-like DNA structures. A series of four-arm junctions are used as vertices within a network of double-helical DNA fragments. Deliberate distortion of the junctions from their most relaxed conformations ensures that a scaffold strand can traverse through individual vertices in multiple directions. DNA gridirons were assembled, ranging from two-dimensional arrays with reconfigurability to multilayer and three-dimensional structures and curved objects.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Han, Dongran -- Pal, Suchetan -- Yang, Yang -- Jiang, Shuoxing -- Nangreave, Jeanette -- Liu, Yan -- Yan, Hao -- New York, N.Y. -- Science. 2013 Mar 22;339(6126):1412-5. doi: 10.1126/science.1232252.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Biodesign Institute, Arizona State University, Tempe, AZ 85287, USA. dongran.han@asu.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23520107" target="_blank"〉PubMed〈/a〉
    Keywords: DNA/*chemistry/*ultrastructure ; Models, Molecular ; *Nanostructures ; Nanotechnology/methods ; *Nucleic Acid Conformation
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 33
    Publication Date: 2013-02-09
    Description: E6 viral oncoproteins are key players in epithelial tumors induced by papillomaviruses in vertebrates, including cervical cancer in humans. E6 proteins target many host proteins by specifically interacting with acidic LxxLL motifs. We solved the crystal structures of bovine (BPV1) and human (HPV16) papillomavirus E6 proteins bound to LxxLL peptides from the focal adhesion protein paxillin and the ubiquitin ligase E6AP, respectively. In both E6 proteins, two zinc domains and a linker helix form a basic-hydrophobic pocket, which captures helical LxxLL motifs in a way compatible with other interaction modes. Mutational inactivation of the LxxLL binding pocket disrupts the oncogenic activities of both E6 proteins. This work reveals the structural basis of both the multifunctionality and the oncogenicity of E6 proteins.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3899395/" 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/PMC3899395/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zanier, Katia -- Charbonnier, Sebastian -- Sidi, Abdellahi Ould M'hamed Ould -- McEwen, Alastair G -- Ferrario, Maria Giovanna -- Poussin-Courmontagne, Pierre -- Cura, Vincent -- Brimer, Nicole -- Babah, Khaled Ould -- Ansari, Tina -- Muller, Isabelle -- Stote, Roland H -- Cavarelli, Jean -- Vande Pol, Scott -- Trave, Gilles -- CA08093/CA/NCI NIH HHS/ -- CA120352/CA/NCI NIH HHS/ -- CA134737/CA/NCI NIH HHS/ -- P30 CA044579/CA/NCI NIH HHS/ -- R01 CA134737/CA/NCI NIH HHS/ -- R01CA134737/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2013 Feb 8;339(6120):694-8. doi: 10.1126/science.1229934.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Biotechnologie et Signalisation Cellulaire UMR 7242, Ecole Superieure de Biotechnologie de Strasbourg, Boulevard Sebastien Brant, BP 10413, F-67412 Illkirch, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23393263" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Motifs ; Amino Acid Sequence ; Bovine papillomavirus 1 ; Crystallography, X-Ray ; Human papillomavirus 16 ; Humans ; Hydrophobic and Hydrophilic Interactions ; Models, Molecular ; Molecular Dynamics Simulation ; Molecular Sequence Data ; Oncogene Proteins, Viral/*chemistry/genetics/*metabolism ; Paxillin/*chemistry/metabolism ; Peptide Fragments/chemistry/metabolism ; Point Mutation ; *Protein Interaction Domains and Motifs ; Protein Structure, Secondary ; Repressor Proteins/*chemistry/genetics/*metabolism ; Ubiquitin-Protein Ligases/*chemistry/metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 34
    Publication Date: 2013-12-07
    Description: Host cell factor-1 (HCF-1), a transcriptional co-regulator of human cell-cycle progression, undergoes proteolytic maturation in which any of six repeated sequences is cleaved by the nutrient-responsive glycosyltransferase, O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT). We report that the tetratricopeptide-repeat domain of O-GlcNAc transferase binds the carboxyl-terminal portion of an HCF-1 proteolytic repeat such that the cleavage region lies in the glycosyltransferase active site above uridine diphosphate-GlcNAc. The conformation is similar to that of a glycosylation-competent peptide substrate. Cleavage occurs between cysteine and glutamate residues and results in a pyroglutamate product. Conversion of the cleavage site glutamate into serine converts an HCF-1 proteolytic repeat into a glycosylation substrate. Thus, protein glycosylation and HCF-1 cleavage occur in the same active site.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3930058/" 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/PMC3930058/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lazarus, Michael B -- Jiang, Jiaoyang -- Kapuria, Vaibhav -- Bhuiyan, Tanja -- Janetzko, John -- Zandberg, Wesley F -- Vocadlo, David J -- Herr, Winship -- Walker, Suzanne -- R01 GM094263/GM/NIGMS NIH HHS/ -- R01GM094263/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2013 Dec 6;342(6163):1235-9. doi: 10.1126/science.1243990.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24311690" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Motifs ; Amino Acid Substitution ; Catalytic Domain ; Crystallography, X-Ray ; Glycosylation ; Host Cell Factor C1/*chemistry/*metabolism ; Humans ; Hydrogen Bonding ; Models, Molecular ; N-Acetylglucosaminyltransferases/*chemistry/*metabolism ; Protein Conformation ; Protein Structure, Tertiary ; Proteolysis ; Pyrrolidonecarboxylic Acid/metabolism ; Recombinant Fusion Proteins/chemistry/metabolism ; Uridine Diphosphate N-Acetylglucosamine/chemistry/metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 35
    Publication Date: 2013-04-13
    Description: An ability to mimic the boundaries of biological compartments would improve our understanding of self-assembly and provide routes to new materials for the delivery of drugs and biologicals and the development of protocells. We show that short designed peptides can be combined to form unilamellar spheres approximately 100 nanometers in diameter. The design comprises two, noncovalent, heterodimeric and homotrimeric coiled-coil bundles. These are joined back to back to render two complementary hubs, which when mixed form hexagonal networks that close to form cages. This design strategy offers control over chemistry, self-assembly, reversibility, and size of such particles.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fletcher, Jordan M -- Harniman, Robert L -- Barnes, Frederick R H -- Boyle, Aimee L -- Collins, Andrew -- Mantell, Judith -- Sharp, Thomas H -- Antognozzi, Massimo -- Booth, Paula J -- Linden, Noah -- Miles, Mervyn J -- Sessions, Richard B -- Verkade, Paul -- Woolfson, Derek N -- BB/G008833/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2013 May 3;340(6132):595-9. doi: 10.1126/science.1233936. Epub 2013 Apr 11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉School of Chemistry, Cantock's Close, University of Bristol, Bristol BS8 1TS, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23579496" target="_blank"〉PubMed〈/a〉
    Keywords: Circular Dichroism ; Microscopy, Electron, Scanning ; Models, Molecular ; Molecular Dynamics Simulation ; *Nanostructures ; Peptides/*chemistry ; Protein Conformation ; Protein Folding ; Protein Multimerization ; Protein Structure, Secondary ; Thermodynamics
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 36
    facet.materialart.
    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2013-01-26
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Forrest, Lucy R -- New York, N.Y. -- Science. 2013 Jan 25;339(6118):399-401. doi: 10.1126/science.1228465.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Computational Structural Biology Group, Max Planck Institute of Biophysics, Max-von-Laue-Strasse 3, 60438 Frankfurt am Main, Germany. lucy.forrest@biophys.mpg.de〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23349276" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Biological Transport ; Cell Membrane/chemistry ; Ion Channels/chemistry/metabolism ; Membrane Transport Proteins/*chemistry/metabolism ; Models, Molecular ; Protein Conformation ; Protein Folding ; Protein Multimerization ; Protein Structure, Secondary
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 37
    Publication Date: 2013-03-09
    Description: RNA chaperones are ubiquitous, heterogeneous proteins essential for RNA structural biogenesis and function. We investigated the mechanism of chaperone-mediated RNA folding by following the time-resolved dimerization of the packaging domain of a retroviral RNA at nucleotide resolution. In the absence of the nucleocapsid (NC) chaperone, dimerization proceeded through multiple, slow-folding intermediates. In the presence of NC, dimerization occurred rapidly through a single structural intermediate. The RNA binding domain of heterogeneous nuclear ribonucleoprotein A1 protein, a structurally unrelated chaperone, also accelerated dimerization. Both chaperones interacted primarily with guanosine residues. Replacing guanosine with more weakly pairing inosine yielded an RNA that folded rapidly without a facilitating chaperone. These results show that RNA chaperones can simplify RNA folding landscapes by weakening intramolecular interactions involving guanosine and explain many RNA chaperone activities.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4338410/" 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/PMC4338410/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Grohman, Jacob K -- Gorelick, Robert J -- Lickwar, Colin R -- Lieb, Jason D -- Bower, Brian D -- Znosko, Brent M -- Weeks, Kevin M -- GM031819/GM/NIGMS NIH HHS/ -- GM064803/GM/NIGMS NIH HHS/ -- GM072518/GM/NIGMS NIH HHS/ -- HHSN261200800001E/PHS HHS/ -- R01 GM031819/GM/NIGMS NIH HHS/ -- R01 GM064803/GM/NIGMS NIH HHS/ -- T32 GM007092/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2013 Apr 12;340(6129):190-5. doi: 10.1126/science.1230715. Epub 2013 Mar 7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry, University of North Carolina, Chapel Hill, NC 27599-3290, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23470731" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; Dimerization ; Guanosine/chemistry/*metabolism ; Heterogeneous-Nuclear Ribonucleoprotein Group A-B/chemistry/metabolism ; Inosine/chemistry/metabolism ; Kinetics ; Models, Molecular ; Molecular Chaperones/chemistry/*metabolism ; Moloney murine leukemia virus/genetics/*metabolism ; Nucleic Acid Conformation ; Nucleocapsid Proteins/chemistry/*metabolism ; Protein Binding ; RNA, Viral/*chemistry/metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 38
    Publication Date: 2013-12-07
    Description: The 2013 outbreak of avian-origin H7N9 influenza in eastern China has raised concerns about its ability to transmit in the human population. The hemagglutinin glycoprotein of most human H7N9 viruses carries Leu(226), a residue linked to adaptation of H2N2 and H3N2 pandemic viruses to human receptors. However, glycan array analysis of the H7 hemagglutinin reveals negligible binding to humanlike alpha2-6-linked receptors and strong preference for a subset of avian-like alpha2-3-linked glycans recognized by all avian H7 viruses. Crystal structures of H7N9 hemagglutinin and six hemagglutinin-glycan complexes have elucidated the structural basis for preferential recognition of avian-like receptors. These findings suggest that the current human H7N9 viruses are poorly adapted for efficient human-to-human transmission.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3954636/" 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/PMC3954636/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Xu, Rui -- de Vries, Robert P -- Zhu, Xueyong -- Nycholat, Corwin M -- McBride, Ryan -- Yu, Wenli -- Paulson, James C -- Wilson, Ian A -- GM62116/GM/NIGMS NIH HHS/ -- P41GM103393/GM/NIGMS NIH HHS/ -- P41RR001209/RR/NCRR NIH HHS/ -- R56 AI099275/AI/NIAID NIH HHS/ -- Y1-CO-1020/CO/NCI NIH HHS/ -- Y1-GM-1104/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2013 Dec 6;342(6163):1230-5. doi: 10.1126/science.1243761.〈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/24311689" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Binding Sites ; Birds ; Carbohydrate Conformation ; Crystallography, X-Ray ; Hemagglutinin Glycoproteins, Influenza Virus/*chemistry/*metabolism ; Humans ; Influenza A Virus, H7N9 Subtype/*metabolism/*pathogenicity ; Influenza in Birds/transmission/virology ; Influenza, Human/transmission/virology ; Ligands ; Microarray Analysis ; Models, Molecular ; Molecular Sequence Data ; Mutation ; Polysaccharides/chemistry/*metabolism ; Receptors, Virus/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
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 39
    Publication Date: 2013-05-04
    Description: Recent studies have identified several mutations in the hemagglutinin (HA) protein that allow the highly pathogenic avian H5N1 influenza A virus to transmit between mammals by airborne route. Here, we determined the complex structures of wild-type and mutant HAs derived from an Indonesia H5N1 virus bound to either avian or human receptor sialic acid analogs. A cis/trans conformational change in the glycosidic linkage of the receptor analog was observed, which explains how the H5N1 virus alters its receptor-binding preference. Furthermore, the mutant HA possessed low affinities for both avian and human receptors. Our findings provide a structural and biophysical basis for the H5N1 adaptation to acquire human, but maintain avian, receptor-binding properties.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhang, Wei -- Shi, Yi -- Lu, Xishan -- Shu, Yuelong -- Qi, Jianxun -- Gao, George F -- New York, N.Y. -- Science. 2013 Jun 21;340(6139):1463-7. doi: 10.1126/science.1236787. Epub 2013 May 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23641058" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Binding Sites ; Birds ; Carbohydrate Conformation ; Crystallography, X-Ray ; Hemagglutinin Glycoproteins, Influenza Virus/*chemistry/genetics/*metabolism ; Humans ; Influenza A Virus, H5N1 Subtype ; Models, Molecular ; Mutant Proteins/chemistry/metabolism ;