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  • Protein Conformation  (248)
  • American Association for the Advancement of Science (AAAS)  (248)
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  • 101
    Publikationsdatum: 2013-03-23
    Beschreibung: 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〉
    Schlagwort(e): 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
    Digitale ISSN: 1095-9203
    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 102
    Publikationsdatum: 2013-08-31
    Beschreibung: MraY (phospho-MurNAc-pentapeptide translocase) is an integral membrane enzyme that catalyzes an essential step of bacterial cell wall biosynthesis: the transfer of the peptidoglycan precursor phospho-MurNAc-pentapeptide to the lipid carrier undecaprenyl phosphate. MraY has long been considered a promising target for the development of antibiotics, but the lack of a structure has hindered mechanistic understanding of this critical enzyme and the enzyme superfamily in general. The superfamily includes enzymes involved in bacterial lipopolysaccharide/teichoic acid formation and eukaryotic N-linked glycosylation, modifications that are central in many biological processes. We present the crystal structure of MraY from Aquifex aeolicus (MraYAA) at 3.3 A resolution, which allows us to visualize the overall architecture, locate Mg(2+) within the active site, and provide a structural basis of catalysis for this class of enzyme.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3906829/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3906829/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chung, Ben C -- Zhao, Jinshi -- Gillespie, Robert A -- Kwon, Do-Yeon -- Guan, Ziqiang -- Hong, Jiyong -- Zhou, Pei -- Lee, Seok-Yong -- AI-55588/AI/NIAID NIH HHS/ -- GM-069338/GM/NIGMS NIH HHS/ -- GM-51310/GM/NIGMS NIH HHS/ -- R01 AI055588/AI/NIAID NIH HHS/ -- R01 GM051310/GM/NIGMS NIH HHS/ -- R01 GM100984/GM/NIGMS NIH HHS/ -- U54 GM069338/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2013 Aug 30;341(6149):1012-6. doi: 10.1126/science.1236501.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, Duke University Medical Center, Durham, NC 27710, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23990562" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Bacteria/*enzymology ; Bacterial Proteins/*chemistry/genetics ; Catalytic Domain ; Cell Wall/*chemistry/enzymology ; Crystallography, X-Ray ; Cytoplasm/enzymology ; Membrane Proteins/*chemistry/genetics ; Periplasm/enzymology ; Protein Conformation ; Protein Structure, Secondary ; Transferases/*chemistry/genetics
    Print ISSN: 0036-8075
    Digitale ISSN: 1095-9203
    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 103
    Publikationsdatum: 2013-03-23
    Beschreibung: 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〉
    Schlagwort(e): 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
    Digitale ISSN: 1095-9203
    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 104
    Publikationsdatum: 2013-05-25
    Beschreibung: The introduction of sulfa drugs for the chemotherapy of bacterial infections in 1935 revolutionized medicine. Although their mechanism of action is understood, the molecular bases for most of their side effects remain obscure. Here, we report that sulfamethoxazole and other sulfa drugs interfere with tetrahydrobiopterin biosynthesis through inhibition of sepiapterin reductase. Crystal structures of sepiapterin reductase with bound sulfa drugs reveal how structurally diverse sulfa drugs achieve specific inhibition of the enzyme. The effect of sulfa drugs on tetrahydrobiopterin-dependent neurotransmitter biosynthesis in cell-based assays provides a rationale for some of their central nervous system-related side effects, particularly in high-dose sulfamethoxazole therapy of Pneumocystis pneumonia. Our findings reveal an unexpected aspect of the pharmacology of sulfa drugs and might translate into their improved medical use.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Haruki, Hirohito -- Pedersen, Miriam Gronlund -- Gorska, Katarzyna Irena -- Pojer, Florence -- Johnsson, Kai -- New York, N.Y. -- Science. 2013 May 24;340(6135):987-91. doi: 10.1126/science.1232972.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉EPFL, Institute of Chemical Sciences and Engineering, Institute of Bioengineering, National Centre of Competence in Research in Chemical Biology, 1015 Lausanne, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23704574" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): 5-Hydroxytryptophan/biosynthesis ; Adult ; Alcohol Oxidoreductases/*antagonists & inhibitors/*chemistry ; Anti-Infective Agents/adverse effects/*pharmacology/therapeutic use ; Biopterin/*analogs & derivatives/biosynthesis ; Cell Line ; Central Nervous System/drug effects ; Crystallography, X-Ray ; Fibroblasts/drug effects/metabolism ; Humans ; Levodopa/biosynthesis ; NADP/chemistry ; Nausea/chemically induced ; Pneumonia, Pneumocystis/drug therapy ; Protein Conformation ; Structure-Activity Relationship ; Sulfamethoxazole/adverse effects/*pharmacology/therapeutic use ; Trimethoprim, Sulfamethoxazole Drug Combination/pharmacology/therapeutic use ; Vomiting/chemically induced
    Print ISSN: 0036-8075
    Digitale ISSN: 1095-9203
    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 105
    Publikationsdatum: 2013-12-07
    Beschreibung: 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〉
    Schlagwort(e): 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
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 106
    Publikationsdatum: 2013-03-30
    Beschreibung: Mutations in the nuclear membrane zinc metalloprotease ZMPSTE24 lead to diseases of lamin processing (laminopathies), such as the premature aging disease progeria and metabolic disorders. ZMPSTE24 processes prelamin A, a component of the nuclear lamina intermediate filaments, by cleaving it at two sites. Failure of this processing results in accumulation of farnesylated, membrane-associated prelamin A. The 3.4 angstrom crystal structure of human ZMPSTE24 has a seven transmembrane alpha-helical barrel structure, surrounding a large, water-filled, intramembrane chamber, capped by a zinc metalloprotease domain with the catalytic site facing into the chamber. The 3.8 angstrom structure of a complex with a CSIM tetrapeptide showed that the mode of binding of the substrate resembles that of an insect metalloprotease inhibitor in thermolysin. Laminopathy-associated mutations predicted to reduce ZMPSTE24 activity map to the zinc metalloprotease peptide-binding site and to the bottom of the chamber.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Quigley, Andrew -- Dong, Yin Yao -- Pike, Ashley C W -- Dong, Liang -- Shrestha, Leela -- Berridge, Georgina -- Stansfeld, Phillip J -- Sansom, Mark S P -- Edwards, Aled M -- Bountra, Chas -- von Delft, Frank -- Bullock, Alex N -- Burgess-Brown, Nicola A -- Carpenter, Elisabeth P -- 092809/Wellcome Trust/United Kingdom -- Canadian Institutes of Health Research/Canada -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2013 Mar 29;339(6127):1604-7. doi: 10.1126/science.1231513.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Structural Genomics Consortium, University of Oxford, Oxford, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23539603" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Amino Acid Sequence ; Catalytic Domain ; Crystallography, X-Ray ; Humans ; Lamin Type A ; Membrane Proteins/*chemistry/genetics ; Metabolism, Inborn Errors/genetics/*metabolism ; Metalloendopeptidases/*chemistry/genetics ; Molecular Sequence Data ; Nuclear Proteins/chemistry/genetics/*metabolism ; Progeria/genetics/metabolism ; Protein Conformation ; Protein Precursors/chemistry/genetics/*metabolism ; Substrate Specificity ; Thermolysin/chemistry
    Print ISSN: 0036-8075
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 107
    Publikationsdatum: 2013-04-13
    Beschreibung: Scaffold-assisted signaling cascades guide cellular decision-making. In budding yeast, one such signal transduction pathway called the mitotic exit network (MEN) governs the transition from mitosis to the G1 phase of the cell cycle. The MEN is conserved and in metazoans is known as the Hippo tumor-suppressor pathway. We found that signaling through the MEN kinase cascade was mediated by an unusual two-step process. The MEN kinase Cdc15 first phosphorylated the scaffold Nud1. This created a phospho-docking site on Nud1, to which the effector kinase complex Dbf2-Mob1 bound through a phosphoserine-threonine binding domain, in order to be activated by Cdc15. This mechanism of pathway activation has implications for signal transmission through other kinase cascades and might represent a general principle in scaffold-assisted signaling.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3884217/" 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/PMC3884217/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rock, Jeremy M -- Lim, Daniel -- Stach, Lasse -- Ogrodowicz, Roksana W -- Keck, Jamie M -- Jones, Michele H -- Wong, Catherine C L -- Yates, John R 3rd -- Winey, Mark -- Smerdon, Stephen J -- Yaffe, Michael B -- Amon, Angelika -- CA112967/CA/NCI NIH HHS/ -- ES015339/ES/NIEHS NIH HHS/ -- F32 GM086038/GM/NIGMS NIH HHS/ -- GM056800/GM/NIGMS NIH HHS/ -- GM51312/GM/NIGMS NIH HHS/ -- MC_U117584228/Medical Research Council/United Kingdom -- P30 CA014051/CA/NCI NIH HHS/ -- P41 GM103533/GM/NIGMS NIH HHS/ -- P41 RR011823/RR/NCRR NIH HHS/ -- R01 ES015339/ES/NIEHS NIH HHS/ -- R01 GM051312/GM/NIGMS NIH HHS/ -- R01 GM056800/GM/NIGMS NIH HHS/ -- R29 GM056800/GM/NIGMS NIH HHS/ -- U117584228/Medical Research Council/United Kingdom -- U54 CA112967/CA/NCI NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2013 May 17;340(6134):871-5. doi: 10.1126/science.1235822. Epub 2013 Apr 11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23579499" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Anaphase ; Cell Cycle Proteins/chemistry/*metabolism ; Deoxyribonucleases/chemistry/*metabolism ; Enzyme Activation ; GTP-Binding Proteins/*metabolism ; *Mitosis ; Phosphoproteins/chemistry/*metabolism ; Phosphorylation ; Protein Conformation ; Protein-Serine-Threonine Kinases/*metabolism ; Saccharomyces cerevisiae/cytology/*metabolism ; Saccharomyces cerevisiae Proteins/chemistry/*metabolism ; Signal Transduction ; tRNA Methyltransferases/chemistry/*metabolism
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 108
    Publikationsdatum: 2013-01-05
    Beschreibung: The ubiquitin system regulates virtually all aspects of cellular function. We report a method to target the myriad enzymes that govern ubiquitination of protein substrates. We used massively diverse combinatorial libraries of ubiquitin variants to develop inhibitors of four deubiquitinases (DUBs) and analyzed the DUB-inhibitor complexes with crystallography. We extended the selection strategy to the ubiquitin conjugating (E2) and ubiquitin ligase (E3) enzymes and found that ubiquitin variants can also enhance enzyme activity. Last, we showed that ubiquitin variants can bind selectively to ubiquitin-binding domains. Ubiquitin variants exhibit selective function in cells and thus enable orthogonal modulation of specific enzymatic steps in the ubiquitin system.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3815447/" 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/PMC3815447/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ernst, Andreas -- Avvakumov, George -- Tong, Jiefei -- Fan, Yihui -- Zhao, Yanling -- Alberts, Philipp -- Persaud, Avinash -- Walker, John R -- Neculai, Ana-Mirela -- Neculai, Dante -- Vorobyov, Andrew -- Garg, Pankaj -- Beatty, Linda -- Chan, Pak-Kei -- Juang, Yu-Chi -- Landry, Marie-Claude -- Yeh, Christina -- Zeqiraj, Elton -- Karamboulas, Konstantina -- Allali-Hassani, Abdellah -- Vedadi, Masoud -- Tyers, Mike -- Moffat, Jason -- Sicheri, Frank -- Pelletier, Laurence -- Durocher, Daniel -- Raught, Brian -- Rotin, Daniela -- Yang, Jianhua -- Moran, Michael F -- Dhe-Paganon, Sirano -- Sidhu, Sachdev S -- 092076/Wellcome Trust/United Kingdom -- 092381/Wellcome Trust/United Kingdom -- 1R01NS072420-01/Canadian Institutes of Health Research/Canada -- MOP-102536/Canadian Institutes of Health Research/Canada -- MOP-111149/Canadian Institutes of Health Research/Canada -- MOP-13494/Canadian Institutes of Health Research/Canada -- MOP-57795/Canadian Institutes of Health Research/Canada -- R01 NS072420/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2013 Feb 1;339(6119):590-5. doi: 10.1126/science.1230161. Epub 2013 Jan 3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Terrence Donnelly Center for Cellular and Biomolecular Research, University of Toronto, 160 College Street, Toronto, Ontario, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23287719" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Amino Acid Sequence ; *Combinatorial Chemistry Techniques ; Conserved Sequence ; Drug Design ; Endopeptidases/chemistry/*metabolism ; HEK293 Cells ; Humans ; Molecular Sequence Data ; Protease Inhibitors/chemistry/*isolation & purification/pharmacology ; Protein Conformation ; Protein Structure, Secondary ; Small Molecule Libraries ; Ubiquitin/chemistry/genetics/*metabolism ; Ubiquitin Thiolesterase/chemistry/*metabolism ; Ubiquitin-Conjugating Enzymes/chemistry/metabolism ; Ubiquitin-Protein Ligases/chemistry/metabolism ; Ubiquitination/*drug effects
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 109
    Publikationsdatum: 2014-03-29
    Beschreibung: 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〉
    Schlagwort(e): 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
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 110
    Publikationsdatum: 2014-03-08
    Beschreibung: 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〉
    Schlagwort(e): 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
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 111
    Publikationsdatum: 2014-04-26
    Beschreibung: 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〉
    Schlagwort(e): 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
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 112
    facet.materialart.
    Unbekannt
    American Association for the Advancement of Science (AAAS)
    Publikationsdatum: 2014-03-08
    Beschreibung: 〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4117199/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4117199/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rosenberg, Susan M -- Queitsch, Christine -- DP1 CA174424/CA/NCI NIH HHS/ -- DP1-CA174424/CA/NCI NIH HHS/ -- DP2 OD008371/OD/NIH HHS/ -- DP2-OD008371/OD/NIH HHS/ -- R01 CA085777/CA/NCI NIH HHS/ -- R01 GM053158/GM/NIGMS NIH HHS/ -- R01-CA85777/CA/NCI NIH HHS/ -- R01-GM53158/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2014 Mar 7;343(6175):1088-9. doi: 10.1126/science.1247472.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Departments of Molecular and Human Genetics, Biochemistry and Molecular Biology, Molecular Virology and Microbiology, and Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24604189" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Antineoplastic Agents/pharmacology/*therapeutic use ; Biodiversity ; DNA Replication/drug effects ; *Evolution, Molecular ; HSP90 Heat-Shock Proteins/metabolism ; Humans ; Mutagenesis ; Neoplasm Invasiveness ; Neoplasm Metastasis/drug therapy ; Neoplasms/blood supply/*drug therapy/*genetics ; Neovascularization, Pathologic/drug therapy ; Protein Conformation
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 113
    facet.materialart.
    Unbekannt
    American Association for the Advancement of Science (AAAS)
    Publikationsdatum: 2014-12-17
    Beschreibung: Despite recent advances, the structures of many proteins cannot be determined by electron cryomicroscopy because the individual proteins move during irradiation. This blurs the images so that they cannot be aligned with each other to calculate a three-dimensional density. Much of this movement stems from instabilities in the carbon substrates used to support frozen samples in the microscope. Here we demonstrate a gold specimen support that nearly eliminates substrate motion during irradiation. This increases the subnanometer image contrast such that alpha helices of individual proteins are resolved. With this improvement, we determine the structure of apoferritin, a smooth octahedral shell of alpha-helical subunits that is particularly difficult to solve by electron microscopy. This advance in substrate design will enable the solution of currently intractable protein structures.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4296556/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4296556/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Russo, Christopher J -- Passmore, Lori A -- 261151/European Research Council/International -- MC_U105192715/Medical Research Council/United Kingdom -- U105192715/Medical Research Council/United Kingdom -- New York, N.Y. -- Science. 2014 Dec 12;346(6215):1377-80. doi: 10.1126/science.1259530.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Medical Research Council (MRC) Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK. ; Medical Research Council (MRC) Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK. passmore@mrc-lmb.cam.ac.uk.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25504723" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Animals ; Apoferritins/*chemistry/*ultrastructure ; Cryoelectron Microscopy/instrumentation/*methods ; Crystallography, X-Ray ; *Gold ; Horses ; Image Processing, Computer-Assisted ; Protein Conformation ; Protein Multimerization ; Protein Structure, Secondary ; Ribosomes/*ultrastructure
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 114
    Publikationsdatum: 2014-10-04
    Beschreibung: Human mitochondrial ribosomes are highly divergent from all other known ribosomes and are specialized to exclusively translate membrane proteins. They are linked with hereditary mitochondrial diseases and are often the unintended targets of various clinically useful antibiotics. Using single-particle cryogenic electron microscopy, we have determined the structure of its large subunit to 3.4 angstrom resolution, revealing 48 proteins, 21 of which are specific to mitochondria. The structure unveils an adaptation of the exit tunnel for hydrophobic nascent peptides, extensive remodeling of the central protuberance, including recruitment of mitochondrial valine transfer RNA (tRNA(Val)) to play an integral structural role, and changes in the tRNA binding sites related to the unusual characteristics of mitochondrial tRNAs.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4246062/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4246062/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Brown, Alan -- Amunts, Alexey -- Bai, Xiao-chen -- Sugimoto, Yoichiro -- Edwards, Patricia C -- Murshudov, Garib -- Scheres, Sjors H W -- Ramakrishnan, V -- 096570/Wellcome Trust/United Kingdom -- MC_U105184332/Medical Research Council/United Kingdom -- MC_UP_A025_1012/Medical Research Council/United Kingdom -- MC_UP_A025_1013/Medical Research Council/United Kingdom -- WT096570/Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2014 Nov 7;346(6210):718-22. doi: 10.1126/science.1258026. Epub 2014 Oct 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Medical Research Council, Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK. ; Medical Research Council, Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK. ramak@mrc-lmb.cam.ac.uk.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25278503" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Binding Sites ; Cryoelectron Microscopy ; Humans ; Mitochondria/genetics/*metabolism ; Mitochondrial Proteins/chemistry/ultrastructure ; Mutation ; Nucleic Acid Conformation ; Protein Conformation ; RNA, Transfer, Val/analysis/*chemistry ; Ribosome Subunits/*chemistry/genetics/*ultrastructure
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 115
    Publikationsdatum: 2010-07-24
    Beschreibung: The ubiquinol-cytochrome c oxidoreductases, central to cellular respiration and photosynthesis, are homodimers. High symmetry has frustrated resolution of whether cross-dimer interactions are functionally important. This has resulted in a proliferation of contradictory models. Here, we duplicated and fused cytochrome b subunits, and then broke symmetry by introducing independent mutations into each monomer. Electrons moved freely within and between monomers, crossing an electron-transfer bridge between two hemes in the core of the dimer. This revealed an H-shaped electron-transfer system that distributes electrons between four quinone oxidation-reduction terminals at the corners of the dimer within the millisecond time scale of enzymatic turnover. Free and unregulated distribution of electrons acts like a molecular-scale bus bar, a design often exploited in electronics.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4073802/" 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/PMC4073802/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Swierczek, Monika -- Cieluch, Ewelina -- Sarewicz, Marcin -- Borek, Arkadiusz -- Moser, Christopher C -- Dutton, P Leslie -- Osyczka, Artur -- 076488/Wellcome Trust/United Kingdom -- R01 GM027309/GM/NIGMS NIH HHS/ -- R01 GM041048/GM/NIGMS NIH HHS/ -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2010 Jul 23;329(5990):451-4. doi: 10.1126/science.1190899.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biophysics, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20651150" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Bacterial Proteins/chemistry/genetics/metabolism ; Cytochromes c/metabolism ; *Electron Transport ; Electron Transport Complex III/*chemistry/genetics/*metabolism ; *Electrons ; Models, Molecular ; Mutant Proteins/chemistry/metabolism ; Oxidation-Reduction ; Point Mutation ; Protein Conformation ; Protein Multimerization ; Protein Subunits/chemistry/metabolism ; Rhodobacter capsulatus/*enzymology ; Ubiquinone/analogs & derivatives/metabolism
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 116
    facet.materialart.
    Unbekannt
    American Association for the Advancement of Science (AAAS)
    Publikationsdatum: 2010-01-02
    Beschreibung: Many bacterial cells contain proteinaceous microcompartments that act as simple organelles by sequestering specific metabolic processes involving volatile or toxic metabolites. Here we report the three-dimensional (3D) crystal structures, with resolutions between 1.65 and 2.5 angstroms, of the four homologous proteins (EutS, EutL, EutK, and EutM) that are thought to be the major shell constituents of a functionally complex ethanolamine utilization (Eut) microcompartment. The Eut microcompartment is used to sequester the metabolism of ethanolamine in bacteria such as Escherichia coli and Salmonella enterica. The four Eut shell proteins share an overall similar 3D fold, but they have distinguishing structural features that help explain the specific roles they play in the microcompartment. For example, EutL undergoes a conformational change that is probably involved in gating molecular transport through shell protein pores, whereas structural evidence suggests that EutK might bind a nucleic acid component. Together these structures give mechanistic insight into bacterial microcompartments.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tanaka, Shiho -- Sawaya, Michael R -- Yeates, Todd O -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2010 Jan 1;327(5961):81-4. doi: 10.1126/science.1179513.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry and Biochemistry, University of California Los Angeles, 611 Charles Young Drive East, Los Angeles, CA 90095, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20044574" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Amino Acid Sequence ; *Cell Compartmentation ; Crystallography, X-Ray ; Escherichia coli K12/*chemistry/*metabolism/ultrastructure ; Escherichia coli Proteins/*chemistry/metabolism ; Ethanolamine/*metabolism ; Metabolic Networks and Pathways ; Models, Molecular ; Molecular Sequence Data ; Polyproteins/*chemistry/metabolism ; Protein Conformation ; Protein Folding ; Protein Structure, Quaternary ; Protein Structure, Tertiary ; Protein Subunits/chemistry/metabolism
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 117
    Publikationsdatum: 2010-04-03
    Beschreibung: Voltage sensors regulate the conformations of voltage-dependent ion channels and enzymes. Their nearly switchlike response as a function of membrane voltage comes from the movement of positively charged amino acids, arginine or lysine, across the membrane field. We used mutations with natural and unnatural amino acids, electrophysiological recordings, and x-ray crystallography to identify a charge transfer center in voltage sensors that facilitates this movement. This center consists of a rigid cyclic "cap" and two negatively charged amino acids to interact with a positive charge. Specific mutations induce a preference for lysine relative to arginine. By placing lysine at specific locations, the voltage sensor can be stabilized in different conformations, which enables a dissection of voltage sensor movements and their relation to ion channel opening.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2869078/" 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/PMC2869078/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tao, Xiao -- Lee, Alice -- Limapichat, Walrati -- Dougherty, Dennis A -- MacKinnon, Roderick -- GM43949/GM/NIGMS NIH HHS/ -- NS 34407/NS/NINDS NIH HHS/ -- P30 EB009998/EB/NIBIB NIH HHS/ -- R01 GM043949/GM/NIGMS NIH HHS/ -- R01 GM043949-20/GM/NIGMS NIH HHS/ -- R37 NS034407/NS/NINDS NIH HHS/ -- R37 NS034407-15/NS/NINDS NIH HHS/ -- R37 NS034407-15S1/NS/NINDS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2010 Apr 2;328(5974):67-73. doi: 10.1126/science.1185954.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Molecular Neurobiology and Biophysics, Rockefeller University, Howard Hughes Medical Institute, 1230 York Avenue, New York, NY 10065, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20360102" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Amino Acid Sequence ; Amino Acid Substitution ; Animals ; Arginine/chemistry ; Binding Sites ; Crystallography, X-Ray ; Electric Capacitance ; *Ion Channel Gating ; Kv1.2 Potassium Channel/*chemistry/*metabolism ; Lysine/chemistry ; Models, Molecular ; Molecular Sequence Data ; Patch-Clamp Techniques ; Phenylalanine/chemistry ; Protein Conformation ; Rats ; Recombinant Fusion Proteins/chemistry/metabolism ; Shab Potassium Channels/*chemistry/*metabolism ; Shaker Superfamily of Potassium Channels/chemistry/metabolism ; Tryptophan/chemistry ; Xenopus laevis
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 118
    Publikationsdatum: 2010-08-28
    Beschreibung: Construction of a complex virus may involve a hierarchy of assembly elements. Here, we report the structure of the whole human adenovirus virion at 3.6 angstroms resolution by cryo-electron microscopy (cryo-EM), revealing in situ atomic models of three minor capsid proteins (IIIa, VIII, and IX), extensions of the (penton base and hexon) major capsid proteins, and interactions within three protein-protein networks. One network is mediated by protein IIIa at the vertices, within group-of-six (GOS) tiles--a penton base and its five surrounding hexons. Another is mediated by ropes (protein IX) that lash hexons together to form group-of-nine (GON) tiles and bind GONs to GONs. The third, mediated by IIIa and VIII, binds each GOS to five surrounding GONs. Optimization of adenovirus for cancer and gene therapy could target these networks.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3412078/" 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/PMC3412078/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Liu, Hongrong -- Jin, Lei -- Koh, Sok Boon S -- Atanasov, Ivo -- Schein, Stan -- Wu, Lily -- Zhou, Z Hong -- 1S10RR23057/RR/NCRR NIH HHS/ -- AI069015/AI/NIAID NIH HHS/ -- CA101904/CA/NCI NIH HHS/ -- GM071940/GM/NIGMS NIH HHS/ -- R01 AI069015/AI/NIAID NIH HHS/ -- R01 CA101904/CA/NCI NIH HHS/ -- R01 GM071940/GM/NIGMS NIH HHS/ -- S10 RR023057/RR/NCRR NIH HHS/ -- New York, N.Y. -- Science. 2010 Aug 27;329(5995):1038-43. doi: 10.1126/science.1187433.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles (UCLA), Los Angeles, CA 90095-7364, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20798312" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Adenoviruses, Human/*chemistry/genetics/metabolism/*ultrastructure ; Capsid/chemistry/ultrastructure ; Capsid Proteins/*chemistry/metabolism/ultrastructure ; Cryoelectron Microscopy ; Genome, Viral ; Image Processing, Computer-Assisted ; Models, Molecular ; Protein Binding ; Protein Conformation ; Protein Interaction Domains and Motifs ; Protein Multimerization ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Virion/chemistry/ultrastructure
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 119
    Publikationsdatum: 2011-01-06
    Beschreibung: Activation of the complement cascade induces inflammatory responses and marks cells for immune clearance. In the central complement-amplification step, a complex consisting of surface-bound C3b and factor B is cleaved by factor D to generate active convertases on targeted surfaces. We present crystal structures of the pro-convertase C3bB at 4 angstrom resolution and its complex with factor D at 3.5 angstrom resolution. Our data show how factor B binding to C3b forms an open "activation" state of C3bB. Factor D specifically binds the open conformation of factor B through a site distant from the catalytic center and is activated by the substrate, which displaces factor D's self-inhibitory loop. This concerted proteolytic mechanism, which is cofactor-dependent and substrate-induced, restricts complement amplification to C3b-tagged target cells.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3087196/" 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/PMC3087196/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Forneris, Federico -- Ricklin, Daniel -- Wu, Jin -- Tzekou, Apostolia -- Wallace, Rachel S -- Lambris, John D -- Gros, Piet -- AI030040/AI/NIAID NIH HHS/ -- AI068730/AI/NIAID NIH HHS/ -- AI072106/AI/NIAID NIH HHS/ -- GM062134/GM/NIGMS NIH HHS/ -- P01 AI068730/AI/NIAID NIH HHS/ -- P01 AI068730-04/AI/NIAID NIH HHS/ -- R01 AI030040/AI/NIAID NIH HHS/ -- R01 AI030040-14/AI/NIAID NIH HHS/ -- R01 AI072106/AI/NIAID NIH HHS/ -- R01 AI072106-04/AI/NIAID NIH HHS/ -- R01 GM062134/GM/NIGMS NIH HHS/ -- R01 GM062134-08/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2010 Dec 24;330(6012):1816-20. doi: 10.1126/science.1195821.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Crystal and Structural Chemistry, Bijvoet Center for Biomolecular Research, Department of Chemistry, Faculty of Science, Utrecht University, Padualaan 8, 3584 CH Utrecht, Netherlands.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21205667" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Binding Sites ; Catalytic Domain ; Complement C3 Convertase, Alternative Pathway/*chemistry/metabolism ; Complement C3b/*chemistry/metabolism ; Complement Factor B/*chemistry/metabolism ; Complement Factor D/*chemistry/metabolism ; Complement Pathway, Alternative ; Crystallography, X-Ray ; Humans ; Models, Molecular ; Mutant Proteins/chemistry ; Protein Binding ; Protein Conformation ; Protein Structure, Tertiary
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  • 120
    Publikationsdatum: 2010-07-10
    Beschreibung: During HIV-1 infection, antibodies are generated against the region of the viral gp120 envelope glycoprotein that binds CD4, the primary receptor for HIV-1. Among these antibodies, VRC01 achieves broad neutralization of diverse viral strains. We determined the crystal structure of VRC01 in complex with a human immunodeficiency virus HIV-1 gp120 core. VRC01 partially mimics CD4 interaction with gp120. A shift from the CD4-defined orientation, however, focuses VRC01 onto the vulnerable site of initial CD4 attachment, allowing it to overcome the glycan and conformational masking that diminishes the neutralization potency of most CD4-binding-site antibodies. To achieve this recognition, VRC01 contacts gp120 mainly through immunoglobulin V-gene regions substantially altered from their genomic precursors. Partial receptor mimicry and extensive affinity maturation thus facilitate neutralization of HIV-1 by natural human antibodies.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2981354/" 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/PMC2981354/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhou, Tongqing -- Georgiev, Ivelin -- Wu, Xueling -- Yang, Zhi-Yong -- Dai, Kaifan -- Finzi, Andres -- Kwon, Young Do -- Scheid, Johannes F -- Shi, Wei -- Xu, Ling -- Yang, Yongping -- Zhu, Jiang -- Nussenzweig, Michel C -- Sodroski, Joseph -- Shapiro, Lawrence -- Nabel, Gary J -- Mascola, John R -- Kwong, Peter D -- P30 AI060354/AI/NIAID NIH HHS/ -- Z99 AI999999/Intramural NIH HHS/ -- New York, N.Y. -- Science. 2010 Aug 13;329(5993):811-7. doi: 10.1126/science.1192819. Epub 2010 Jul 8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda, MD 20892, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20616231" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): AIDS Vaccines ; Amino Acid Sequence ; Antibodies, Neutralizing/*chemistry/*immunology ; Antibody Affinity ; Antigenic Variation ; Antigens, CD4/chemistry/immunology/metabolism ; Base Sequence ; Binding Sites, Antibody ; Crystallography, X-Ray ; Epitopes/immunology ; HIV Antibodies/*chemistry/*immunology ; HIV Envelope Protein gp120/chemistry/genetics/*immunology ; HIV-1/*immunology ; Humans ; Immunoglobulin Fab Fragments/chemistry/immunology/metabolism ; Models, Molecular ; Molecular Mimicry ; Molecular Sequence Data ; Neutralization Tests ; Protein Conformation ; Protein Structure, Tertiary
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 121
    Publikationsdatum: 2010-04-17
    Beschreibung: SAGA is a transcriptional coactivator complex that is conserved across eukaryotes and performs multiple functions during transcriptional activation and elongation. One role is deubiquitination of histone H2B, and this activity resides in a distinct subcomplex called the deubiquitinating module (DUBm), which contains the ubiquitin-specific protease Ubp8, bound to Sgf11, Sus1, and Sgf73. The deubiquitinating activity depends on the presence of all four DUBm proteins. We report here the 1.90 angstrom resolution crystal structure of the DUBm bound to ubiquitin aldehyde, as well as the 2.45 angstrom resolution structure of the uncomplexed DUBm. The structure reveals an arrangement of protein domains that gives rise to a highly interconnected complex, which is stabilized by eight structural zinc atoms that are critical for enzymatic activity. The structure suggests a model for how interactions with the other DUBm proteins activate Ubp8 and allows us to speculate about how the DUBm binds to monoubiquitinated histone H2B in nucleosomes.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220450/" 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/PMC4220450/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Samara, Nadine L -- Datta, Ajit B -- Berndsen, Christopher E -- Zhang, Xiangbin -- Yao, Tingting -- Cohen, Robert E -- Wolberger, Cynthia -- F32GM089037/GM/NIGMS NIH HHS/ -- R01 GM095822/GM/NIGMS NIH HHS/ -- Y1-CO-1020/CO/NCI NIH HHS/ -- Y1-GM-1104/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2010 May 21;328(5981):1025-9. doi: 10.1126/science.1190049. Epub 2010 Apr 15.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biophysics and Biophysical Chemistry, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20395473" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Aldehydes/chemistry/metabolism ; Crystallography, X-Ray ; Endopeptidases/*chemistry/metabolism ; Histone Acetyltransferases/*chemistry/metabolism ; Histones/metabolism ; Models, Biological ; Models, Molecular ; Nuclear Proteins/*chemistry/metabolism ; Nucleosomes/chemistry/metabolism ; Protein Binding ; Protein Conformation ; Protein Structure, Tertiary ; RNA-Binding Proteins/*chemistry/metabolism ; Saccharomyces cerevisiae Proteins/*chemistry/metabolism ; Trans-Activators/*chemistry/metabolism ; Transcription Factors/*chemistry/metabolism ; Ubiquitin/chemistry/*metabolism ; Ubiquitinated Proteins/metabolism ; Ubiquitination ; Ubiquitins/chemistry/metabolism ; Zinc/chemistry/metabolism ; Zinc Fingers
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 122
    facet.materialart.
    Unbekannt
    American Association for the Advancement of Science (AAAS)
    Publikationsdatum: 2010-03-27
    Beschreibung: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cohen, Jon -- New York, N.Y. -- Science. 2010 Mar 26;327(5973):1563-4. doi: 10.1126/science.327.5973.1563.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20339037" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Amino Acid Sequence ; Animals ; Antibodies, Neutralizing/immunology ; Antibodies, Viral/immunology ; Disease Outbreaks ; *Evolution, Molecular ; Genetic Drift ; Glycosylation ; *Hemagglutinin Glycoproteins, Influenza Virus/chemistry/genetics/immunology ; Humans ; *Influenza A Virus, H1N1 Subtype/chemistry/genetics/immunology ; Influenza Vaccines ; Influenza, Human/epidemiology/immunology/*virology ; Mice ; Models, Molecular ; Protein Conformation
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 123
    Publikationsdatum: 2010-06-19
    Beschreibung: Pharmaceutical synthesis can benefit greatly from the selectivity gains associated with enzymatic catalysis. Here, we report an efficient biocatalytic process to replace a recently implemented rhodium-catalyzed asymmetric enamine hydrogenation for the large-scale manufacture of the antidiabetic compound sitagliptin. Starting from an enzyme that had the catalytic machinery to perform the desired chemistry but lacked any activity toward the prositagliptin ketone, we applied a substrate walking, modeling, and mutation approach to create a transaminase with marginal activity for the synthesis of the chiral amine; this variant was then further engineered via directed evolution for practical application in a manufacturing setting. The resultant biocatalysts showed broad applicability toward the synthesis of chiral amines that previously were accessible only via resolution. This work underscores the maturation of biocatalysis to enable efficient, economical, and environmentally benign processes for the manufacture of pharmaceuticals.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Savile, Christopher K -- Janey, Jacob M -- Mundorff, Emily C -- Moore, Jeffrey C -- Tam, Sarena -- Jarvis, William R -- Colbeck, Jeffrey C -- Krebber, Anke -- Fleitz, Fred J -- Brands, Jos -- Devine, Paul N -- Huisman, Gjalt W -- Hughes, Gregory J -- New York, N.Y. -- Science. 2010 Jul 16;329(5989):305-9. doi: 10.1126/science.1188934. Epub 2010 Jun 17.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Codexis, Incorporated, 200 Penobscot Drive, Redwood City, CA 94063, USA. christopher.savile@codexis.com〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20558668" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Amines/*chemical synthesis ; Biocatalysis ; Catalytic Domain ; *Directed Molecular Evolution ; Hypoglycemic Agents/*chemical synthesis/metabolism ; Ketones/*chemistry/metabolism ; Models, Molecular ; Molecular Structure ; Mutagenesis ; Protein Conformation ; *Protein Engineering ; Pyrazines/*chemical synthesis/metabolism ; Sitagliptin Phosphate ; Solubility ; Stereoisomerism ; Substrate Specificity ; Transaminases/*chemistry/genetics/metabolism ; Triazoles/*chemical synthesis/metabolism
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 124
    Publikationsdatum: 2010-07-03
    Beschreibung: Therapeutic efforts to restore biosynthetic processing of the cystic fibrosis transmembrane conductance regulator lacking the F508 residue (DeltaF508CFTR) are hampered by ubiquitin-dependent lysosomal degradation of nonnative, rescued DeltaF508CFTR from the plasma membrane. Here, functional small interfering RNA screens revealed the contribution of chaperones, cochaperones, and ubiquitin-conjugating and -ligating enzymes to the elimination of unfolded CFTR from the cell surface, as part of a peripheral protein quality-control system. Ubiquitination of nonnative CFTR was required for efficient internalization and lysosomal degradation. This peripheral protein quality-control mechanism probably participates in the preservation of cellular homeostasis by degrading damaged plasma membrane proteins that have escaped from the endoplasmic reticulum quality control or are generated by environmental stresses in situ.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Okiyoneda, Tsukasa -- Barriere, Herve -- Bagdany, Miklos -- Rabeh, Wael M -- Du, Kai -- Hohfeld, Jorg -- Young, Jason C -- Lukacs, Gergely L -- Canadian Institutes of Health Research/Canada -- New York, N.Y. -- Science. 2010 Aug 13;329(5993):805-10. doi: 10.1126/science.1191542. Epub 2010 Jul 1.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physiology, and Groupe de Recherche Axe sur la Structure des Proteine (GRASP) McGill University, Montreal, Quebec H3G 1Y6, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20595578" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Cell Membrane/*metabolism ; Cystic Fibrosis Transmembrane Conductance ; Regulator/*chemistry/genetics/*metabolism ; Glycosylation ; HSC70 Heat-Shock Proteins/genetics/metabolism ; HSP90 Heat-Shock Proteins/metabolism ; HeLa Cells ; Homeostasis ; Humans ; Lysosomes/metabolism ; Molecular Chaperones/metabolism ; Mutant Proteins/chemistry/metabolism ; Protein Conformation ; *Protein Folding ; Protein Stability ; Protein Transport ; RNA, Small Interfering ; Recombinant Proteins/metabolism ; Temperature ; Ubiquitin-Protein Ligases/genetics/metabolism ; Ubiquitinated Proteins/chemistry/metabolism ; Ubiquitination
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 125
    facet.materialart.
    Unbekannt
    American Association for the Advancement of Science (AAAS)
    Publikationsdatum: 2010-05-29
    Beschreibung: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Collinge, John -- MC_U123192748/Medical Research Council/United Kingdom -- New York, N.Y. -- Science. 2010 May 28;328(5982):1111-2. doi: 10.1126/science.1190815.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉MRC Prion Unit, Institute of Neurology, University College London, London WC1N3BG, UK. j.collinge@prion.ucl.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20508117" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Animals ; *Deer ; Evolution, Molecular ; Mutation ; Polymorphism, Genetic ; PrPC Proteins/*chemistry/genetics ; PrPSc Proteins/*chemistry/genetics/pathogenicity ; Protein Conformation ; Protein Folding ; Selection, Genetic ; Species Specificity ; *Wasting Disease, Chronic/transmission
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  • 126
    facet.materialart.
    Unbekannt
    American Association for the Advancement of Science (AAAS)
    Publikationsdatum: 2010-07-31
    Beschreibung: Alkanes, the major constituents of gasoline, diesel, and jet fuel, are naturally produced by diverse species; however, the genetics and biochemistry behind this biology have remained elusive. Here we describe the discovery of an alkane biosynthesis pathway from cyanobacteria. The pathway consists of an acyl-acyl carrier protein reductase and an aldehyde decarbonylase, which together convert intermediates of fatty acid metabolism to alkanes and alkenes. The aldehyde decarbonylase is related to the broadly functional nonheme diiron enzymes. Heterologous expression of the alkane operon in Escherichia coli leads to the production and secretion of C13 to C17 mixtures of alkanes and alkenes. These genes and enzymes can now be leveraged for the simple and direct conversion of renewable raw materials to fungible hydrocarbon fuels.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schirmer, Andreas -- Rude, Mathew A -- Li, Xuezhi -- Popova, Emanuela -- del Cardayre, Stephen B -- New York, N.Y. -- Science. 2010 Jul 30;329(5991):559-62. doi: 10.1126/science.1187936.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉LS9, Inc., 600 Gateway Boulevard, South San Francisco, CA 94080, USA. aschirmer@ls9.com〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20671186" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Acyl Carrier Protein/metabolism ; Aldehyde-Lyases/chemistry/genetics/*metabolism ; Aldehydes/metabolism ; Alkanes/*metabolism ; Alkenes/metabolism ; Bacterial Proteins/chemistry/genetics/metabolism ; Biosynthetic Pathways ; Cyanobacteria/enzymology/*genetics/metabolism ; Escherichia coli/*genetics/metabolism ; Fatty Acids/metabolism ; Fatty Alcohols/metabolism ; *Genes, Bacterial ; Operon ; Oxidoreductases/genetics/*metabolism ; Protein Conformation ; Recombinant Proteins/genetics/metabolism ; Substrate Specificity ; Synechococcus/enzymology/*genetics/*metabolism
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 127
    facet.materialart.
    Unbekannt
    American Association for the Advancement of Science (AAAS)
    Publikationsdatum: 2010-03-13
    Beschreibung: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bollinger, J Martin Jr -- Matthews, Megan L -- New York, N.Y. -- Science. 2010 Mar 12;327(5971):1337-8. doi: 10.1126/science.1187421.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry, Pennsylvania State University, University Park, PA 16802, USA. jmb21@psu.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20223975" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Catalytic Domain ; Enzyme Precursors/*chemistry/*metabolism ; Hemeproteins/chemistry/*metabolism ; Hydroxylation ; Indolequinones/*metabolism ; Models, Chemical ; Oxidation-Reduction ; Oxidoreductases Acting on CH-NH Group Donors/*chemistry/*metabolism ; Protein Binding ; Protein Conformation ; *Protein Processing, Post-Translational ; Tryptophan/*analogs & derivatives/chemistry/metabolism
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 128
    Publikationsdatum: 2010-05-29
    Beschreibung: Host defense peptides such as defensins are components of innate immunity and have retained antibiotic activity throughout evolution. Their activity is thought to be due to amphipathic structures, which enable binding and disruption of microbial cytoplasmic membranes. Contrary to this, we show that plectasin, a fungal defensin, acts by directly binding the bacterial cell-wall precursor Lipid II. A wide range of genetic and biochemical approaches identify cell-wall biosynthesis as the pathway targeted by plectasin. In vitro assays for cell-wall synthesis identified Lipid II as the specific cellular target. Consistently, binding studies confirmed the formation of an equimolar stoichiometric complex between Lipid II and plectasin. Furthermore, key residues in plectasin involved in complex formation were identified using nuclear magnetic resonance spectroscopy and computational modeling.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schneider, Tanja -- Kruse, Thomas -- Wimmer, Reinhard -- Wiedemann, Imke -- Sass, Vera -- Pag, Ulrike -- Jansen, Andrea -- Nielsen, Allan K -- Mygind, Per H -- Raventos, Dorotea S -- Neve, Soren -- Ravn, Birthe -- Bonvin, Alexandre M J J -- De Maria, Leonardo -- Andersen, Anders S -- Gammelgaard, Lora K -- Sahl, Hans-Georg -- Kristensen, Hans-Henrik -- New York, N.Y. -- Science. 2010 May 28;328(5982):1168-72. doi: 10.1126/science.1185723.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Pharmaceutical Microbiology Section, Institute for Medical Microbiology, Immunology, and Parasitology, University of Bonn, D-53115 Bonn, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20508130" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Anti-Bacterial Agents/pharmacology ; Ascomycota/chemistry ; Bacillus subtilis/drug effects/growth & development/*metabolism/ultrastructure ; Binding Sites ; Cell Membrane/metabolism ; Cell Wall/*metabolism ; Computer Simulation ; Defensins/*metabolism/pharmacology ; Fungal Proteins/*metabolism/pharmacology ; Models, Molecular ; Nuclear Magnetic Resonance, Biomolecular ; Oligonucleotide Array Sequence Analysis ; Peptides/*metabolism/pharmacology ; Protein Conformation ; Staphylococcus/drug effects/growth & development/*metabolism/ultrastructure ; Uridine Diphosphate N-Acetylmuramic Acid/*analogs & derivatives/metabolism ; Vancomycin/pharmacology
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 129
    Publikationsdatum: 2010-04-24
    Beschreibung: Bacterial NusG is a highly conserved transcription factor that is required for most Rho activity in vivo. We show by nuclear magnetic resonance spectroscopy that Escherichia coli NusG carboxyl-terminal domain forms a complex alternatively with Rho or with transcription factor NusE, a protein identical to 30S ribosomal protein S10. Because NusG amino-terminal domain contacts RNA polymerase and the NusG carboxy-terminal domain interaction site of NusE is accessible in the ribosomal 30S subunit, NusG may act as a link between transcription and translation. Uncoupling of transcription and translation at the ends of bacterial operons enables transcription termination by Rho factor, and competition between ribosomal NusE and Rho for NusG helps to explain why Rho cannot terminate translated transcripts.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Burmann, Bjorn M -- Schweimer, Kristian -- Luo, Xiao -- Wahl, Markus C -- Stitt, Barbara L -- Gottesman, Max E -- Rosch, Paul -- GM037219/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2010 Apr 23;328(5977):501-4. doi: 10.1126/science.1184953.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Lehrstuhl Biopolymere und Forschungszentrum fur Bio-Makromolekule, Universitat Bayreuth, Universitatsstrasse 30, 95447 Bayreuth, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20413501" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Amino Acid Sequence ; Binding Sites ; Binding, Competitive ; DNA-Directed RNA Polymerases/metabolism ; Escherichia coli/genetics/*metabolism ; Escherichia coli Proteins/biosynthesis/chemistry/*genetics/metabolism ; Hydrophobic and Hydrophilic Interactions ; Models, Molecular ; Molecular Sequence Data ; Nuclear Magnetic Resonance, Biomolecular ; Operon ; Peptide Elongation Factors/chemistry/*metabolism ; Protein Binding ; *Protein Biosynthesis ; Protein Conformation ; Protein Interaction Domains and Motifs ; Protein Structure, Tertiary ; Ribosomal Proteins/chemistry/*metabolism ; Ribosome Subunits, Small, Bacterial/metabolism ; Transcription Factors/chemistry/*metabolism ; *Transcription, Genetic
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 130
    Publikationsdatum: 2010-09-11
    Beschreibung: Proteins can sample conformational states that are critical for function but are seldom detected directly because of their low occupancies and short lifetimes. In this work, we used chemical shifts and bond-vector orientation constraints obtained from nuclear magnetic resonance relaxation dispersion spectroscopy, in concert with a chemical shift-based method for structure elucidation, to determine an atomic-resolution structure of an "invisible" folding intermediate of a small protein module: the FF domain. The structure reveals non-native elements preventing formation of the native conformation in the carboxyl-terminal part of the protein. This is consistent with the kinetics of folding in which a well-structured intermediate forms rapidly and then rearranges slowly to the native state. The approach introduces a general strategy for structure determination of low-populated and transiently formed protein states.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Korzhnev, Dmitry M -- Religa, Tomasz L -- Banachewicz, Wiktor -- Fersht, Alan R -- Kay, Lewis E -- MC_U105484373/Medical Research Council/United Kingdom -- Canadian Institutes of Health Research/Canada -- New York, N.Y. -- Science. 2010 Sep 10;329(5997):1312-6. doi: 10.1126/science.1191723.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Genetics, the University of Toronto, Toronto, Ontario M5S 1A8, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20829478" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Carrier Proteins/*chemistry ; Computational Biology ; Kinetics ; Models, Molecular ; Nuclear Magnetic Resonance, Biomolecular ; Protein Conformation ; *Protein Folding ; Protein Structure, Secondary ; *Protein Structure, Tertiary ; Software ; Thermodynamics
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  • 131
    facet.materialart.
    Unbekannt
    American Association for the Advancement of Science (AAAS)
    Publikationsdatum: 2010-11-13
    Beschreibung: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kim, Jungsu -- Holtzman, David M -- New York, N.Y. -- Science. 2010 Nov 12;330(6006):918-9. doi: 10.1126/science.1198314.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurology, Hope Center for Neurological Disorders, Knight Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, MO 63110, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21071652" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Alzheimer Disease/metabolism/pathology ; Amyloid beta-Peptides/administration & dosage/*chemistry/metabolism ; Amyloidosis/metabolism/pathology ; Animals ; Brain/blood supply/metabolism/*pathology ; Cerebral Amyloid Angiopathy/metabolism/pathology ; Mice ; Plaque, Amyloid/metabolism/*pathology ; Prions/chemistry/metabolism ; Protein Conformation ; Protein Folding
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 132
    facet.materialart.
    Unbekannt
    American Association for the Advancement of Science (AAAS)
    Publikationsdatum: 2010-07-10
    Beschreibung: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Weyand, Simone -- Iwata, So -- New York, N.Y. -- Science. 2010 Jul 9;329(5988):151-2. doi: 10.1126/science.1192680.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Molecular Biosciences, Membrane Protein Crystallography Group, Imperial College, London SW7 2AZ, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20616256" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Animals ; Binding Sites ; Calcium/*metabolism ; Humans ; *Ion Channel Gating ; Large-Conductance Calcium-Activated Potassium Channels/*chemistry/*metabolism ; Models, Molecular ; Protein Conformation ; Protein Structure, Tertiary
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  • 133
    Publikationsdatum: 2010-11-06
    Beschreibung: The dose-limiting side effect of the common colon cancer chemotherapeutic CPT-11 is severe diarrhea caused by symbiotic bacterial beta-glucuronidases that reactivate the drug in the gut. We sought to target these enzymes without killing the commensal bacteria essential for human health. Potent bacterial beta-glucuronidase inhibitors were identified by high-throughput screening and shown to have no effect on the orthologous mammalian enzyme. Crystal structures established that selectivity was based on a loop unique to bacterial beta-glucuronidases. Inhibitors were highly effective against the enzyme target in living aerobic and anaerobic bacteria, but did not kill the bacteria or harm mammalian cells. Finally, oral administration of an inhibitor protected mice from CPT-11-induced toxicity. Thus, drugs may be designed to inhibit undesirable enzyme activities in essential microbial symbiotes to enhance chemotherapeutic efficacy.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3110694/" 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/PMC3110694/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wallace, Bret D -- Wang, Hongwei -- Lane, Kimberly T -- Scott, John E -- Orans, Jillian -- Koo, Ja Seol -- Venkatesh, Madhukumar -- Jobin, Christian -- Yeh, Li-An -- Mani, Sridhar -- Redinbo, Matthew R -- CA127231/CA/NCI NIH HHS/ -- CA98468/CA/NCI NIH HHS/ -- R01 CA127231/CA/NCI NIH HHS/ -- R01 CA127231-01A2/CA/NCI NIH HHS/ -- R01 CA127231-02/CA/NCI NIH HHS/ -- R01 CA127231-03/CA/NCI NIH HHS/ -- R01 CA161879/CA/NCI NIH HHS/ -- R01 DK073338/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 2010 Nov 5;330(6005):831-5. doi: 10.1126/science.1191175.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry, University of North Carolina, Chapel Hill, NC 27599, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21051639" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Animals ; Antineoplastic Agents, Phytogenic/metabolism/*toxicity ; Bacteria, Anaerobic/drug effects ; Camptothecin/*analogs & derivatives/metabolism/toxicity ; Cell Line, Tumor ; Colon/drug effects/microbiology/pathology ; Crystallography, X-Ray ; Diarrhea/prevention & control ; Drug Evaluation, Preclinical ; Enzyme Inhibitors/chemistry/metabolism/*pharmacology ; Escherichia coli/enzymology ; Escherichia coli Proteins/antagonists & inhibitors/chemistry/isolation & ; purification/metabolism ; Female ; Glucuronidase/*antagonists & inhibitors/chemistry/isolation & ; purification/metabolism/*pharmacology ; Humans ; Intestinal Mucosa/drug effects/microbiology/pathology ; Mice ; Mice, Inbred BALB C ; Models, Molecular ; Prodrugs/metabolism/toxicity ; Protein Conformation
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 134
    Publikationsdatum: 2010-11-27
    Beschreibung: Nitric oxide reductase (NOR) is an iron-containing enzyme that catalyzes the reduction of nitric oxide (NO) to generate a major greenhouse gas, nitrous oxide (N(2)O). Here, we report the crystal structure of NOR from Pseudomonas aeruginosa at 2.7 angstrom resolution. The structure reveals details of the catalytic binuclear center. The non-heme iron (Fe(B)) is coordinated by three His and one Glu ligands, but a His-Tyr covalent linkage common in cytochrome oxidases (COX) is absent. This structural characteristic is crucial for NOR reaction. Although the overall structure of NOR is closely related to COX, neither the D- nor K-proton pathway, which connect the COX active center to the intracellular space, was observed. Protons required for the NOR reaction are probably provided from the extracellular side.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hino, Tomoya -- Matsumoto, Yushi -- Nagano, Shingo -- Sugimoto, Hiroshi -- Fukumori, Yoshihiro -- Murata, Takeshi -- Iwata, So -- Shiro, Yoshitsugu -- New York, N.Y. -- Science. 2010 Dec 17;330(6011):1666-70. doi: 10.1126/science.1195591. Epub 2010 Nov 25.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉RIKEN SPring-8 Center, 1-1-1 Kouto, Sayo, Hyogo 679-5148, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21109633" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Amino Acid Sequence ; Bacterial Proteins/chemistry/metabolism ; Catalytic Domain ; Crystallography, X-Ray ; Cytochromes c/chemistry ; Electron Transport ; Electron Transport Complex IV/chemistry/metabolism ; Heme/chemistry ; Hydrogen Bonding ; Hydrophobic and Hydrophilic Interactions ; Iron/chemistry ; Membrane Proteins/chemistry/metabolism ; Models, Molecular ; Molecular Sequence Data ; Nitric Oxide/*metabolism ; Nitrous Oxide/*metabolism ; Oxidation-Reduction ; Oxidoreductases/*chemistry/*metabolism ; Protein Conformation ; Protein Multimerization ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Protein Subunits ; Protons ; Pseudomonas aeruginosa/*enzymology/metabolism
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 135
    Publikationsdatum: 2010-10-30
    Beschreibung: According to the prion hypothesis, atypical phenotypes arise when a prion protein adopts an alternative conformation and persist when that form assembles into self-replicating aggregates. Amyloid formation in vitro provides a model for this protein-misfolding pathway, but the mechanism by which this process interacts with the cellular environment to produce transmissible phenotypes is poorly understood. Using the yeast prion Sup35/[PSI(+)], we found that protein conformation determined the size distribution of aggregates through its interactions with a molecular chaperone. Shifts in this range created variations in aggregate abundance among cells because of a size threshold for transmission, and this heterogeneity, along with aggregate growth and fragmentation, induced age-dependent fluctuations in phenotype. Thus, prion conformations may specify phenotypes as population averages in a dynamic system.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3003433/" 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/PMC3003433/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Derdowski, Aaron -- Sindi, Suzanne S -- Klaips, Courtney L -- DiSalvo, Susanne -- Serio, Tricia R -- AG032818/AG/NIA NIH HHS/ -- AG034754/AG/NIA NIH HHS/ -- GM069802/GM/NIGMS NIH HHS/ -- GM085976/GM/NIGMS NIH HHS/ -- GM089049/GM/NIGMS NIH HHS/ -- R01 GM069802/GM/NIGMS NIH HHS/ -- R01 GM069802-05/GM/NIGMS NIH HHS/ -- T32 GM007601/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2010 Oct 29;330(6004):680-3. doi: 10.1126/science.1197785.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology, Cell Biology and Biochemistry, Brown University, 185 Meeting Street, Post Office Box G-L2, Providence, RI 02912, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21030659" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Algorithms ; Cell Division ; Computer Simulation ; Peptide Termination Factors/*chemistry/metabolism ; Phenotype ; Prions/*chemistry/metabolism ; Protein Conformation ; Protein Folding ; Recombinant Fusion Proteins/chemistry ; Saccharomyces cerevisiae/*chemistry/cytology ; Saccharomyces cerevisiae Proteins/*chemistry/metabolism
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 136
    Publikationsdatum: 2010-05-01
    Beschreibung: Photosynthetic reaction centers convert the energy content of light into a transmembrane potential difference and so provide the major pathway for energy input into the biosphere. We applied time-resolved Laue diffraction to study light-induced conformational changes in the photosynthetic reaction center complex of Blastochloris viridis. The side chain of TyrL162, which lies adjacent to the special pair of bacteriochlorophyll molecules that are photooxidized in the primary light conversion event of photosynthesis, was observed to move 1.3 angstroms closer to the special pair after photoactivation. Free energy calculations suggest that this movement results from the deprotonation of this conserved tyrosine residue and provides a mechanism for stabilizing the primary charge separation reactions of photosynthesis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wohri, Annemarie B -- Katona, Gergely -- Johansson, Linda C -- Fritz, Emelie -- Malmerberg, Erik -- Andersson, Magnus -- Vincent, Jonathan -- Eklund, Mattias -- Cammarata, Marco -- Wulff, Michael -- Davidsson, Jan -- Groenhof, Gerrit -- Neutze, Richard -- New York, N.Y. -- Science. 2010 Apr 30;328(5978):630-3. doi: 10.1126/science.1186159.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemical and Biological Engineering, Chalmers University of Technology, Box 462, SE-40530 Goteborg, Sweden.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20431017" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Bacterial Proteins/*chemistry/metabolism ; Bacteriochlorophylls/chemistry/metabolism ; Crystallography, X-Ray ; Cytochromes c/chemistry/metabolism ; Electron Transport ; Hydrogen Bonding ; Hydrogen-Ion Concentration ; Hyphomicrobiaceae/*chemistry/metabolism ; *Light ; Models, Molecular ; Molecular Dynamics Simulation ; Oxidation-Reduction ; Photosynthetic Reaction Center Complex Proteins/*chemistry/metabolism ; Protein Conformation ; Protons ; Quinones/chemistry/metabolism ; Thermodynamics
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 137
    facet.materialart.
    Unbekannt
    American Association for the Advancement of Science (AAAS)
    Publikationsdatum: 2010-12-18
    Beschreibung: 〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4012676/" 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/PMC4012676/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Moenne-Loccoz, Pierre -- Fee, James A -- R01 GM035342/GM/NIGMS NIH HHS/ -- R01 GM074785/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2010 Dec 17;330(6011):1632-3. doi: 10.1126/science.1200247.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Environmental & Biomolecular Systems, Institute of Environmental Health, Oregon Health & Science University, Beaverton, OR 97006, USA. ploccoz@ebs.ogi.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21164002" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Bacterial Proteins/chemistry/metabolism ; Catalytic Domain ; Crystallography, X-Ray ; Cytochrome b Group/chemistry/metabolism ; Cytochromes c/chemistry/metabolism ; Electron Transport ; Electron Transport Complex IV/chemistry/metabolism ; Evolution, Molecular ; Heme/chemistry ; Hydrophobic and Hydrophilic Interactions ; Models, Molecular ; Nitric Oxide/*metabolism ; *Nitrogen Cycle ; Nitrous Oxide/*metabolism ; Oxidation-Reduction ; Oxidoreductases/*chemistry/*metabolism ; Protein Conformation ; Protein Folding ; Protein Structure, Secondary ; Protein Subunits ; Protons ; Pseudomonas aeruginosa/*enzymology
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 138
    Publikationsdatum: 2010-08-28
    Beschreibung: Porous materials find widespread application in storage, separation, and catalytic technologies. We report a crystalline porous solid with adaptable porosity, in which a simple dipeptide linker is arranged in a regular array by coordination to metal centers. Experiments reinforced by molecular dynamics simulations showed that low-energy torsions and displacements of the peptides enabled the available pore volume to evolve smoothly from zero as the guest loading increased. The observed cooperative feedback in sorption isotherms resembled the response of proteins undergoing conformational selection, suggesting an energy landscape similar to that required for protein folding. The flexible peptide linker was shown to play the pivotal role in changing the pore conformation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rabone, J -- Yue, Y-F -- Chong, S Y -- Stylianou, K C -- Bacsa, J -- Bradshaw, D -- Darling, G R -- Berry, N G -- Khimyak, Y Z -- Ganin, A Y -- Wiper, P -- Claridge, J B -- Rosseinsky, M J -- New York, N.Y. -- Science. 2010 Aug 27;329(5995):1053-7. doi: 10.1126/science.1190672.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry, University of Liverpool, Liverpool, L69 7ZD, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20798314" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Adsorption ; Carbon Dioxide/*chemistry ; Crystallization ; Diffusion ; Dipeptides/*chemistry ; Hydrogen Bonding ; Ligands ; Magnetic Resonance Spectroscopy ; Models, Molecular ; Molecular Dynamics Simulation ; Molecular Structure ; Physicochemical Processes ; Porosity ; Pressure ; Protein Conformation ; Protein Folding ; Solvents ; Thermodynamics ; X-Ray Diffraction ; Zinc/*chemistry
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 139
    facet.materialart.
    Unbekannt
    American Association for the Advancement of Science (AAAS)
    Publikationsdatum: 2010-08-28
    Beschreibung: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wright, Paul A -- New York, N.Y. -- Science. 2010 Aug 27;329(5995):1025-6. doi: 10.1126/science.1195176.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉School of Chemistry, University of St. Andrews, Purdie Building, North Haugh, St. Andrews, Fife, KY16 9ST, UK. paw2@st-andrews.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20798307" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Adsorption ; Carbon Dioxide/*chemistry ; Dipeptides/*chemistry ; Models, Molecular ; Molecular Structure ; Porosity ; Pressure ; Protein Conformation ; Thermodynamics ; Zinc/*chemistry
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 140
    Publikationsdatum: 2010-04-03
    Beschreibung: The proteasome catalyzes the majority of protein degradation in the cell and plays an integral role in cellular homeostasis. Control over proteolysis by the 20S core-particle (CP) proteasome is achieved by gated access of substrate; thus, an understanding of the molecular mechanism by which these gates regulate substrate entry is critical. We used methyl-transverse relaxation optimized nuclear magnetic resonance spectroscopy to show that the amino-terminal residues that compose the gates of the alpha subunits of the Thermoplasma acidophilum proteasome are highly dynamic over a broad spectrum of time scales and that gating termini are in conformations that extend either well inside (closed gate) or outside (open gate) of the antechamber. Interconversion between these conformers on a time scale of seconds leads to a dynamic regulation of 20S CP proteolysis activity.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Religa, Tomasz L -- Sprangers, Remco -- Kay, Lewis E -- Canadian Institutes of Health Research/Canada -- New York, N.Y. -- Science. 2010 Apr 2;328(5974):98-102. doi: 10.1126/science.1184991.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Genetics, University of Toronto, Toronto, Ontario M5S 1A8, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20360109" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Archaeal Proteins/*chemistry/genetics/*metabolism ; Electron Spin Resonance Spectroscopy ; Endopeptidases/*chemistry/genetics/*metabolism ; Models, Molecular ; Mutant Proteins/chemistry/metabolism ; Nuclear Magnetic Resonance, Biomolecular ; Protein Conformation ; Protein Structure, Quaternary ; Protein Subunits/chemistry/metabolism ; Spin Labels ; Thermoplasma/chemistry/*enzymology/genetics/metabolism
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 141
    Publikationsdatum: 2010-11-26
    Beschreibung: Dopamine modulates movement, cognition, and emotion through activation of dopamine G protein-coupled receptors in the brain. The crystal structure of the human dopamine D3 receptor (D3R) in complex with the small molecule D2R/D3R-specific antagonist eticlopride reveals important features of the ligand binding pocket and extracellular loops. On the intracellular side of the receptor, a locked conformation of the ionic lock and two distinctly different conformations of intracellular loop 2 are observed. Docking of R-22, a D3R-selective antagonist, reveals an extracellular extension of the eticlopride binding site that comprises a second binding pocket for the aryl amide of R-22, which differs between the highly homologous D2R and D3R. This difference provides direction to the design of D3R-selective agents for treating drug abuse and other neuropsychiatric indications.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3058422/" 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/PMC3058422/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chien, Ellen Y T -- Liu, Wei -- Zhao, Qiang -- Katritch, Vsevolod -- Han, Gye Won -- Hanson, Michael A -- Shi, Lei -- Newman, Amy Hauck -- Javitch, Jonathan A -- Cherezov, Vadim -- Stevens, Raymond C -- DA022413/DA/NIDA NIH HHS/ -- DA023694/DA/NIDA NIH HHS/ -- GM075915/GM/NIGMS NIH HHS/ -- K05 DA022413/DA/NIDA NIH HHS/ -- K05 DA022413-05/DA/NIDA NIH HHS/ -- MH54137/MH/NIMH NIH HHS/ -- P50 GM073197/GM/NIGMS NIH HHS/ -- P50 GM073197-07/GM/NIGMS NIH HHS/ -- R00 DA023694/DA/NIDA NIH HHS/ -- R00 DA023694-04/DA/NIDA NIH HHS/ -- R01 GM089857/GM/NIGMS NIH HHS/ -- R01 MH054137/MH/NIMH NIH HHS/ -- R01 MH054137-16/MH/NIMH NIH HHS/ -- R21 RR025336/RR/NCRR NIH HHS/ -- R21 RR025336-01A1/RR/NCRR NIH HHS/ -- U54 GM074961/GM/NIGMS NIH HHS/ -- U54 GM074961-050001/GM/NIGMS NIH HHS/ -- U54 GM094618/GM/NIGMS NIH HHS/ -- U54 GM094618-01/GM/NIGMS NIH HHS/ -- Y1-CO-1020/CO/NCI NIH HHS/ -- Y1-GM-1104/GM/NIGMS NIH HHS/ -- Intramural NIH HHS/ -- New York, N.Y. -- Science. 2010 Nov 19;330(6007):1091-5. doi: 10.1126/science.1197410.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular 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/21097933" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Animals ; Arginine/chemistry ; Binding Sites ; Cell Line ; Crystallography, X-Ray ; Dopamine Antagonists/*chemistry ; Dopamine D2 Receptor Antagonists ; Humans ; Models, Molecular ; Protein Conformation ; Receptors, Dopamine D3/antagonists & inhibitors/*chemistry ; Recombinant Proteins/chemistry ; Salicylamides/*chemistry ; Spodoptera
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  • 142
    Publikationsdatum: 2010-10-30
    Beschreibung: Ribosomes are self-assembling macromolecular machines that translate DNA into proteins, and an understanding of ribosome biogenesis is central to cellular physiology. Previous studies on the Escherichia coli 30S subunit suggest that ribosome assembly occurs via multiple parallel pathways rather than through a single rate-limiting step, but little mechanistic information is known about this process. Discovery single-particle profiling (DSP), an application of time-resolved electron microscopy, was used to obtain more than 1 million snapshots of assembling 30S subunits, identify and visualize the structures of 14 assembly intermediates, and monitor the population flux of these intermediates over time. DSP results were integrated with mass spectrometry data to construct the first ribosome-assembly mechanism that incorporates binding dependencies, rate constants, and structural characterization of populated intermediates.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2990404/" 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/PMC2990404/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mulder, Anke M -- Yoshioka, Craig -- Beck, Andrea H -- Bunner, Anne E -- Milligan, Ronald A -- Potter, Clinton S -- Carragher, Bridget -- Williamson, James R -- GM-52468/GM/NIGMS NIH HHS/ -- P41 RR017573/RR/NCRR NIH HHS/ -- P41 RR017573-10/RR/NCRR NIH HHS/ -- R01 GM052468/GM/NIGMS NIH HHS/ -- R01 GM052468-16/GM/NIGMS NIH HHS/ -- R01 RR023093/RR/NCRR NIH HHS/ -- R01 RR023093-09/RR/NCRR NIH HHS/ -- R37 GM053757/GM/NIGMS NIH HHS/ -- R37 GM053757-16/GM/NIGMS NIH HHS/ -- R37-GM-53757/GM/NIGMS NIH HHS/ -- RR023093/RR/NCRR NIH HHS/ -- RR175173/RR/NCRR NIH HHS/ -- New York, N.Y. -- Science. 2010 Oct 29;330(6004):673-7. doi: 10.1126/science.1193220.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cell Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21030658" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Bacterial Proteins/chemistry/metabolism ; Image Processing, Computer-Assisted ; Kinetics ; Mass Spectrometry ; Microscopy, Electron/methods ; Models, Molecular ; Nucleic Acid Conformation ; Protein Binding ; Protein Conformation ; RNA, Bacterial/chemistry ; RNA, Ribosomal/chemistry ; Ribosomal Proteins/chemistry/*metabolism ; Ribosome Subunits, Small, Bacterial/chemistry/*metabolism/*ultrastructure
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  • 143
    Publikationsdatum: 2010-03-13
    Beschreibung: MauG is a diheme enzyme responsible for the posttranslational modification of two tryptophan residues to form the tryptophan tryptophylquinone (TTQ) cofactor of methylamine dehydrogenase (MADH). MauG converts preMADH, containing monohydroxylated betaTrp57, to fully functional MADH by catalyzing the insertion of a second oxygen atom into the indole ring and covalently linking betaTrp57 to betaTrp108. We have solved the x-ray crystal structure of MauG complexed with preMADH to 2.1 angstroms. The c-type heme irons and the nascent TTQ site are separated by long distances over which electron transfer must occur to achieve catalysis. In addition, one of the hemes has an atypical His-Tyr axial ligation. The crystalline protein complex is catalytically competent; upon addition of hydrogen peroxide, MauG-dependent TTQ synthesis occurs.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2878131/" 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/PMC2878131/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jensen, Lyndal M R -- Sanishvili, Ruslan -- Davidson, Victor L -- Wilmot, Carrie M -- GM41574/GM/NIGMS NIH HHS/ -- GM66569/GM/NIGMS NIH HHS/ -- R01 GM041574/GM/NIGMS NIH HHS/ -- R01 GM041574-20/GM/NIGMS NIH HHS/ -- R01 GM066569/GM/NIGMS NIH HHS/ -- R01 GM066569-08/GM/NIGMS NIH HHS/ -- Y1-CO-1020/CO/NCI NIH HHS/ -- Y1-GM-1104/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2010 Mar 12;327(5971):1392-4. doi: 10.1126/science.1182492.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN 55455, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20223990" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Amino Acid Sequence ; Bacterial Proteins/*chemistry/metabolism ; Biocatalysis ; Catalytic Domain ; Crystallography, X-Ray ; Enzyme Precursors/*chemistry/metabolism ; Hemeproteins/*chemistry/metabolism ; Hydrogen Peroxide/metabolism ; Indolequinones/*chemistry/metabolism ; Ligands ; Models, Molecular ; Molecular Sequence Data ; Oxidoreductases Acting on CH-NH Group Donors/*chemistry/metabolism ; Paracoccus denitrificans/chemistry/enzymology/*metabolism ; Protein Conformation ; *Protein Processing, Post-Translational ; Tryptophan/*analogs & derivatives/chemistry/metabolism
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  • 144
    Publikationsdatum: 2011-07-09
    Beschreibung: Current flu vaccines provide only limited coverage against seasonal strains of influenza viruses. The identification of V(H)1-69 antibodies that broadly neutralize almost all influenza A group 1 viruses constituted a breakthrough in the influenza field. Here, we report the isolation and characterization of a human monoclonal antibody CR8020 with broad neutralizing activity against most group 2 viruses, including H3N2 and H7N7, which cause severe human infection. The crystal structure of Fab CR8020 with the 1968 pandemic H3 hemagglutinin (HA) reveals a highly conserved epitope in the HA stalk distinct from the epitope recognized by the V(H)1-69 group 1 antibodies. Thus, a cocktail of two antibodies may be sufficient to neutralize most influenza A subtypes and, hence, enable development of a universal flu vaccine and broad-spectrum antibody therapies.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3210727/" 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/PMC3210727/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ekiert, Damian C -- Friesen, Robert H E -- Bhabha, Gira -- Kwaks, Ted -- Jongeneelen, Mandy -- Yu, Wenli -- Ophorst, Carla -- Cox, Freek -- Korse, Hans J W M -- Brandenburg, Boerries -- Vogels, Ronald -- Brakenhoff, Just P J -- Kompier, Ronald -- Koldijk, Martin H -- Cornelissen, Lisette A H M -- Poon, Leo L M -- Peiris, Malik -- Koudstaal, Wouter -- Wilson, Ian A -- Goudsmit, Jaap -- GM080209/GM/NIGMS NIH HHS/ -- HHSN272200900060C/PHS HHS/ -- T32 GM080209/GM/NIGMS NIH HHS/ -- T32 GM080209-03/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2011 Aug 12;333(6044):843-50. doi: 10.1126/science.1204839. Epub 2011 Jul 7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology, 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/21737702" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Amino Acid Sequence ; Animals ; Antibodies, Monoclonal/*immunology/isolation & purification ; Antibodies, Neutralizing/*immunology/isolation & purification ; Antibodies, Viral/*immunology/isolation & purification ; Antibody Specificity ; Antigens, Viral/chemistry/genetics/*immunology ; Binding Sites, Antibody ; Conserved Sequence ; Crystallography, X-Ray ; Epitopes/immunology ; Hemagglutinin Glycoproteins, Influenza Virus/chemistry/genetics/*immunology ; Humans ; Influenza A Virus, H3N2 Subtype/immunology ; Influenza A Virus, H7N7 Subtype/genetics/immunology ; Influenza A virus/*immunology ; Influenza Vaccines/immunology ; Influenza, Human/immunology/prevention & control/therapy ; Mice ; Models, Molecular ; Molecular Sequence Data ; Mutation ; Neutralization Tests ; Orthomyxoviridae Infections/immunology/prevention & control ; Protein Conformation
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  • 145
    Publikationsdatum: 2011-10-25
    Beschreibung: The ability of electrospray to propel large viruses into a mass spectrometer is established and is rationalized by analogy to the atmospheric transmission of the common cold. Much less clear is the fate of membrane-embedded molecular machines in the gas phase. Here we show that rotary adenosine triphosphatases (ATPases)/synthases from Thermus thermophilus and Enterococcus hirae can be maintained intact with membrane and soluble subunit interactions preserved in vacuum. Mass spectra reveal subunit stoichiometries and the identity of tightly bound lipids within the membrane rotors. Moreover, subcomplexes formed in solution and gas phases reveal the regulatory effects of nucleotide binding on both ATP hydrolysis and proton translocation. Consequently, we can link specific lipid and nucleotide binding with distinct regulatory roles.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3927129/" 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/PMC3927129/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhou, Min -- Morgner, Nina -- Barrera, Nelson P -- Politis, Argyris -- Isaacson, Shoshanna C -- Matak-Vinkovic, Dijana -- Murata, Takeshi -- Bernal, Ricardo A -- Stock, Daniela -- Robinson, Carol V -- 088150/Wellcome Trust/United Kingdom -- 099141/Wellcome Trust/United Kingdom -- G1000819/Medical Research Council/United Kingdom -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2011 Oct 21;334(6054):380-5. doi: 10.1126/science.1210148.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry, Physical and Theoretical Chemistry Laboratory, University of Oxford, Oxford OX1 3QZ, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22021858" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Adenosine Triphosphatases/*chemistry/*metabolism ; Adenosine Triphosphate/*metabolism ; Bacterial Proteins/*chemistry/*metabolism ; Binding Sites ; Cardiolipins/analysis/metabolism ; Enterococcus/enzymology ; Hydrolysis ; Hydrophobic and Hydrophilic Interactions ; Mass Spectrometry ; Membrane Lipids/analysis/*metabolism ; Models, Molecular ; Phosphatidylethanolamines/analysis/metabolism ; Protein Conformation ; Protein Multimerization ; Protein Structure, Tertiary ; Protein Subunits/chemistry/metabolism ; Spectrometry, Mass, Electrospray Ionization ; Thermus thermophilus/*enzymology ; Vacuolar Proton-Translocating ATPases/*chemistry/*metabolism
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  • 146
    Publikationsdatum: 2011-07-19
    Beschreibung: Fanconi anemia is a cancer predisposition syndrome caused by defects in the repair of DNA interstrand cross-links (ICLs). Central to this pathway is the Fanconi anemia I-Fanconi anemia D2 (FANCI-FANCD2) (ID) complex, which is activated by DNA damage-induced phosphorylation and monoubiquitination. The 3.4 angstrom crystal structure of the ~300 kilodalton ID complex reveals that monoubiquitination and regulatory phosphorylation sites map to the I-D interface, suggesting that they occur on monomeric proteins or an opened-up complex and that they may serve to stabilize I-D heterodimerization. The 7.8 angstrom electron-density map of FANCI-DNA crystals and in vitro data show that each protein has binding sites for both single- and double-stranded DNA, suggesting that the ID complex recognizes DNA structures that result from the encounter of replication forks with an ICL.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3310437/" 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/PMC3310437/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Joo, Woo -- Xu, Guozhou -- Persky, Nicole S -- Smogorzewska, Agata -- Rudge, Derek G -- Buzovetsky, Olga -- Elledge, Stephen J -- Pavletich, Nikola P -- R01 GM044664/GM/NIGMS NIH HHS/ -- R01 GM044664-10/GM/NIGMS NIH HHS/ -- R37 GM044664/GM/NIGMS NIH HHS/ -- T32 CA009216/CA/NCI NIH HHS/ -- T32 CA009216-32/CA/NCI NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2011 Jul 15;333(6040):312-6. doi: 10.1126/science.1205805.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Structural Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21764741" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Amino Acid Sequence ; Animals ; Binding Sites ; Crystallography, X-Ray ; DNA/chemistry/metabolism ; *DNA Repair ; DNA, Single-Stranded/chemistry/metabolism ; Fanconi Anemia/genetics ; Fanconi Anemia Complementation Group D2 Protein/*chemistry/metabolism ; Fanconi Anemia Complementation Group Proteins/*chemistry/metabolism ; Hydrophobic and Hydrophilic Interactions ; Mice ; Models, Molecular ; Molecular Sequence Data ; Phosphorylation ; Protein Binding ; Protein Conformation ; Protein Folding ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Static Electricity ; Ubiquitin/chemistry ; Ubiquitination
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  • 147
    facet.materialart.
    Unbekannt
    American Association for the Advancement of Science (AAAS)
    Publikationsdatum: 2011-03-10
    Beschreibung: Type III secretion systems (T3SSs) are essential virulence factors used by many Gram-negative bacteria to inject proteins that make eukaryotic host cells accessible to invasion. The T3SS core structure, the needle complex (NC), is a ~3.5 megadalton-sized, oligomeric, membrane-embedded complex. Analyzing cryo-electron microscopy images of top views of NCs or NC substructures from Salmonella typhimurium revealed a 24-fold symmetry for the inner rings and a 15-fold symmetry for the outer rings, giving an overall C3 symmetry. Local refinement and averaging showed the organization of the central core and allowed us to reconstruct a subnanometer composite structure of the NC, which together with confident docking of atomic structures reveal insights into its overall organization and structural requirements during assembly.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schraidt, Oliver -- Marlovits, Thomas C -- New York, N.Y. -- Science. 2011 Mar 4;331(6021):1192-5. doi: 10.1126/science.1199358.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Research Institute of Molecular Pathology, Dr. Bohr Gasse 7, A-1030 Vienna, Austria.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21385715" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Bacterial Proteins/*chemistry/ultrastructure ; *Bacterial Secretion Systems ; Cryoelectron Microscopy ; Crystallography, X-Ray ; Image Processing, Computer-Assisted ; Membrane Proteins/*chemistry/ultrastructure ; Membrane Transport Proteins/*chemistry/ultrastructure ; Models, Molecular ; Mutation ; Protein Conformation ; Protein Structure, Tertiary ; Salmonella typhimurium/*chemistry
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  • 148
    Publikationsdatum: 2011-06-18
    Beschreibung: Root hairs are single cells that develop by tip growth and are specialized in the absorption of nutrients. Their cell walls are composed of polysaccharides and hydroxyproline-rich glycoproteins (HRGPs) that include extensins (EXTs) and arabinogalactan-proteins (AGPs). Proline hydroxylation, an early posttranslational modification of HRGPs that is catalyzed by prolyl 4-hydroxylases (P4Hs), defines the subsequent O-glycosylation sites in EXTs (which are mainly arabinosylated) and AGPs (which are mainly arabinogalactosylated). We explored the biological function of P4Hs, arabinosyltransferases, and EXTs in root hair cell growth. Biochemical inhibition or genetic disruption resulted in the blockage of polarized growth in root hairs and reduced arabinosylation of EXTs. Our results demonstrate that correct O-glycosylation on EXTs is essential for cell-wall self-assembly and, hence, root hair elongation in Arabidopsis thaliana.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Velasquez, Silvia M -- Ricardi, Martiniano M -- Dorosz, Javier Gloazzo -- Fernandez, Paula V -- Nadra, Alejandro D -- Pol-Fachin, Laercio -- Egelund, Jack -- Gille, Sascha -- Harholt, Jesper -- Ciancia, Marina -- Verli, Hugo -- Pauly, Markus -- Bacic, Antony -- Olsen, Carl Erik -- Ulvskov, Peter -- Petersen, Bent Larsen -- Somerville, Chris -- Iusem, Norberto D -- Estevez, Jose M -- New York, N.Y. -- Science. 2011 Jun 17;332(6036):1401-3. doi: 10.1126/science.1206657.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Instituto de Fisiologia, Biologia Molecular y Neurociencias-Consejo Nacional de Investigaciones Cientificas y Tecnicas (IFIByNE-CONICET), Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires C1428EGA, Argentina.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21680836" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Arabidopsis/genetics/growth & development/*metabolism ; Arabidopsis Proteins/chemistry/genetics/*metabolism ; Arabinose/metabolism ; Carbohydrate Conformation ; Cell Wall/*metabolism ; Gene Expression Regulation, Plant ; Genes, Plant ; Glycoproteins/chemistry/*metabolism ; Glycosylation ; Glycosyltransferases/genetics/metabolism ; Hydroxylation ; Hydroxyproline/*metabolism ; Models, Biological ; Mutation ; Pentosyltransferases/chemistry/metabolism ; Phenotype ; Plant Proteins/chemistry/*metabolism ; Plant Roots/cytology/*growth & development/metabolism ; Polysaccharides/chemistry ; Procollagen-Proline Dioxygenase/genetics/*metabolism ; Proline/metabolism ; Protein Conformation ; Protein Processing, Post-Translational ; Protein Structure, Secondary
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  • 149
    Publikationsdatum: 2011-05-28
    Beschreibung: There is a general need for the engineering of protein-like molecules that organize into geometrically specific superstructures on molecular surfaces, directing further functionalization to create richly textured, multilayered assemblies. Here we describe a computational approach whereby the surface properties and symmetry of a targeted surface define the sequence and superstructure of surface-organizing peptides. Computational design proceeds in a series of steps that encode both surface recognition and favorable intersubunit packing interactions. This procedure is exemplified in the design of peptides that assemble into a tubular structure surrounding single-walled carbon nanotubes (SWNTs). The geometrically defined, virus-like coating created by these peptides converts the smooth surfaces of SWNTs into highly textured assemblies with long-scale order, capable of directing the assembly of gold nanoparticles into helical arrays along the SWNT axis.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3264056/" 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/PMC3264056/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Grigoryan, Gevorg -- Kim, Yong Ho -- Acharya, Rudresh -- Axelrod, Kevin -- Jain, Rishabh M -- Willis, Lauren -- Drndic, Marija -- Kikkawa, James M -- DeGrado, William F -- 5F32GM084631-02/GM/NIGMS NIH HHS/ -- F32 GM084631/GM/NIGMS NIH HHS/ -- F32 GM084631-02/GM/NIGMS NIH HHS/ -- GM54616/GM/NIGMS NIH HHS/ -- R37 GM054616/GM/NIGMS NIH HHS/ -- R37 GM054616-17/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2011 May 27;332(6033):1071-6. doi: 10.1126/science.1198841.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Biophysics, University of Pennsylvania, Philadelphia, PA 19104, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21617073" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Amino Acid Sequence ; Computer Simulation ; Gold ; Metal Nanoparticles ; Models, Molecular ; *Nanotubes, Carbon ; Peptides/*chemistry ; Protein Binding ; Protein Conformation ; *Protein Engineering ; Protein Stability ; Protein Structure, Secondary ; Solubility ; Surface Properties ; Viruses
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 150
    Publikationsdatum: 2011-03-12
    Beschreibung: Activation of G protein-coupled receptors upon agonist binding is a critical step in the signaling cascade for this family of cell surface proteins. We report the crystal structure of the A(2A) adenosine receptor (A(2A)AR) bound to an agonist UK-432097 at 2.7 angstrom resolution. Relative to inactive, antagonist-bound A(2A)AR, the agonist-bound structure displays an outward tilt and rotation of the cytoplasmic half of helix VI, a movement of helix V, and an axial shift of helix III, resembling the changes associated with the active-state opsin structure. Additionally, a seesaw movement of helix VII and a shift of extracellular loop 3 are likely specific to A(2A)AR and its ligand. The results define the molecule UK-432097 as a "conformationally selective agonist" capable of receptor stabilization in a specific active-state configuration.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3086811/" 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/PMC3086811/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Xu, Fei -- Wu, Huixian -- Katritch, Vsevolod -- Han, Gye Won -- Jacobson, Kenneth A -- Gao, Zhan-Guo -- Cherezov, Vadim -- Stevens, Raymond C -- GM075915/GM/NIGMS NIH HHS/ -- P50 GM073197/GM/NIGMS NIH HHS/ -- R01 GM089857/GM/NIGMS NIH HHS/ -- U54 GM094618/GM/NIGMS NIH HHS/ -- U54 GM094618-01/GM/NIGMS NIH HHS/ -- Y1-CO-1020/CO/NCI NIH HHS/ -- Y1-GM-1104/GM/NIGMS NIH HHS/ -- Intramural NIH HHS/ -- New York, N.Y. -- Science. 2011 Apr 15;332(6027):322-7. doi: 10.1126/science.1202793. Epub 2011 Mar 10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology, 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/21393508" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Adenosine/*analogs & derivatives/chemistry/metabolism ; Adenosine A2 Receptor Agonists/chemistry/*metabolism ; Binding Sites ; Crystallography, X-Ray ; Humans ; Hydrogen Bonding ; Ligands ; Models, Molecular ; Opsins/chemistry/metabolism ; Protein Conformation ; Protein Structure, Secondary ; Receptor, Adenosine A2A/*chemistry/*metabolism ; Rhodopsin/chemistry/metabolism ; Triazines/chemistry/metabolism ; Triazoles/chemistry/metabolism
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  • 151
    Publikationsdatum: 2011-11-05
    Beschreibung: Protein synthesis in all organisms is catalyzed by ribosomes. In comparison to their prokaryotic counterparts, eukaryotic ribosomes are considerably larger and are subject to more complex regulation. The large ribosomal subunit (60S) catalyzes peptide bond formation and contains the nascent polypeptide exit tunnel. We present the structure of the 60S ribosomal subunit from Tetrahymena thermophila in complex with eukaryotic initiation factor 6 (eIF6), cocrystallized with the antibiotic cycloheximide (a eukaryotic-specific inhibitor of protein synthesis), at a resolution of 3.5 angstroms. The structure illustrates the complex functional architecture of the eukaryotic 60S subunit, which comprises an intricate network of interactions between eukaryotic-specific ribosomal protein features and RNA expansion segments. It reveals the roles of eukaryotic ribosomal protein elements in the stabilization of the active site and the extent of eukaryotic-specific differences in other functional regions of the subunit. Furthermore, it elucidates the molecular basis of the interaction with eIF6 and provides a structural framework for further studies of ribosome-associated diseases and the role of the 60S subunit in the initiation of protein synthesis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Klinge, Sebastian -- Voigts-Hoffmann, Felix -- Leibundgut, Marc -- Arpagaus, Sofia -- Ban, Nenad -- New York, N.Y. -- Science. 2011 Nov 18;334(6058):941-8. doi: 10.1126/science.1211204. Epub 2011 Nov 3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Molecular Biology and Biophysics, ETH Zurich, Zurich, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22052974" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Anti-Bacterial Agents/metabolism ; Base Sequence ; Binding Sites ; Crystallization ; Crystallography, X-Ray ; Cycloheximide/metabolism ; Eukaryotic Initiation Factors/*chemistry/metabolism ; Models, Molecular ; Molecular Sequence Data ; Nucleic Acid Conformation ; Peptide Chain Initiation, Translational ; Protein Conformation ; Protein Structure, Secondary ; Protozoan Proteins/chemistry/metabolism ; RNA, Protozoan/chemistry/metabolism ; RNA, Ribosomal/chemistry/metabolism ; RNA, Ribosomal, 5.8S/chemistry/metabolism ; Ribosomal Proteins/*chemistry/metabolism ; Ribosome Subunits, Large, Eukaryotic/*chemistry/metabolism/ultrastructure ; Tetrahymena thermophila/*chemistry/metabolism
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  • 152
    Publikationsdatum: 2011-04-30
    Beschreibung: The radical S-adenosyl-L-methionine (SAM) enzymes RlmN and Cfr methylate 23S ribosomal RNA, modifying the C2 or C8 position of adenosine 2503. The methyl groups are installed by a two-step sequence involving initial methylation of a conserved Cys residue (RlmN Cys(355)) by SAM. Methyl transfer to the substrate requires reductive cleavage of a second equivalent of SAM. Crystal structures of RlmN and RlmN with SAM show that a single molecule of SAM coordinates the [4Fe-4S] cluster. Residue Cys(355) is S-methylated and located proximal to the SAM methyl group, suggesting the SAM that is involved in the initial methyl transfer binds at the same site. Thus, RlmN accomplishes its complex reaction with structural economy, harnessing the two most important reactivities of SAM within a single site.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3506250/" 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/PMC3506250/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Boal, Amie K -- Grove, Tyler L -- McLaughlin, Monica I -- Yennawar, Neela H -- Booker, Squire J -- Rosenzweig, Amy C -- GM58518/GM/NIGMS NIH HHS/ -- GM63847/GM/NIGMS NIH HHS/ -- K99 GM100011/GM/NIGMS NIH HHS/ -- R01 GM058518/GM/NIGMS NIH HHS/ -- R01 GM063847/GM/NIGMS NIH HHS/ -- Y1-CO-1020/CO/NCI NIH HHS/ -- Y1-GM-1104/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2011 May 27;332(6033):1089-92. doi: 10.1126/science.1205358. Epub 2011 Apr 28.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biosciences, Northwestern University, Evanston, IL 60208, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21527678" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Bacterial Proteins/chemistry/metabolism ; Catalytic Domain ; Crystallography, X-Ray ; Cysteine/chemistry ; Escherichia coli/enzymology/growth & development ; Escherichia coli Proteins/*chemistry/*metabolism ; Evolution, Molecular ; Hydrogen Bonding ; Methylation ; Methyltransferases/*chemistry/*metabolism ; Models, Molecular ; Oxidation-Reduction ; Protein Conformation ; Protein Structure, Secondary ; Protein Structure, Tertiary ; RNA, Bacterial/metabolism ; RNA, Ribosomal, 23S/metabolism ; S-Adenosylmethionine/*chemistry/*metabolism
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  • 153
    Publikationsdatum: 2011-10-29
    Beschreibung: Direct observation of the detailed conformational fluctuations of a single protein molecule en route to its folded state has so far been realized only in silico. We have used single-molecule force spectroscopy to study the folding transitions of single calmodulin molecules. High-resolution optical tweezers assays in combination with hidden Markov analysis reveal a complex network of on- and off-pathway intermediates. Cooperative and anticooperative interactions across domain boundaries can be observed directly. The folding network involves four intermediates. Two off-pathway intermediates exhibit non-native interdomain interactions and compete with the ultrafast productive folding pathway.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Stigler, Johannes -- Ziegler, Fabian -- Gieseke, Anja -- Gebhardt, J Christof M -- Rief, Matthias -- New York, N.Y. -- Science. 2011 Oct 28;334(6055):512-6. doi: 10.1126/science.1207598.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Physik Department E22, Technische Universitat Munchen, James-Franck-Strasse, 85748 Garching, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22034433" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Calcium/chemistry ; Calmodulin/*chemistry ; Kinetics ; Markov Chains ; Optical Tweezers ; Protein Conformation ; Protein Folding ; Protein Structure, Tertiary ; Thermodynamics
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  • 154
    Publikationsdatum: 2011-10-25
    Beschreibung: Inhibitor of apoptosis (IAP) proteins are negative regulators of cell death. IAP family members contain RING domains that impart E3 ubiquitin ligase activity. Binding of endogenous or small-molecule antagonists to select baculovirus IAP repeat (BIR) domains within cellular IAP (cIAP) proteins promotes autoubiquitination and proteasomal degradation and so releases inhibition of apoptosis mediated by cIAP. Although the molecular details of antagonist-BIR domain interactions are well understood, it is not clear how this binding event influences the activity of the RING domain. Here biochemical and structural studies reveal that the unliganded, multidomain cIAP1 sequesters the RING domain within a compact, monomeric structure that prevents RING dimerization. Antagonist binding induces conformational rearrangements that enable RING dimerization and formation of the active E3 ligase.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dueber, Erin C -- Schoeffler, Allyn J -- Lingel, Andreas -- Elliott, J Michael -- Fedorova, Anna V -- Giannetti, Anthony M -- Zobel, Kerry -- Maurer, Brigitte -- Varfolomeev, Eugene -- Wu, Ping -- Wallweber, Heidi J A -- Hymowitz, Sarah G -- Deshayes, Kurt -- Vucic, Domagoj -- Fairbrother, Wayne J -- P41RR001209/RR/NCRR NIH HHS/ -- New York, N.Y. -- Science. 2011 Oct 21;334(6054):376-80. doi: 10.1126/science.1207862.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Early Discovery Biochemistry, Genentech, 1 DNA Way, South San Francisco, CA 94080, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22021857" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Amino Acid Sequence ; Animals ; Cell Line ; Cell Line, Tumor ; Cloning, Molecular ; Humans ; Hydrophobic and Hydrophilic Interactions ; Inhibitor of Apoptosis Proteins/*antagonists & inhibitors/*chemistry/metabolism ; Mice ; Models, Biological ; Models, Molecular ; Molecular Sequence Data ; Mutagenesis, Site-Directed ; Proteasome Endopeptidase Complex/metabolism ; Protein Conformation ; Protein Interaction Domains and Motifs ; Protein Multimerization ; Protein Structure, Secondary ; Scattering, Small Angle ; Ubiquitin-Protein Ligases/chemistry/metabolism ; Ubiquitinated Proteins/chemistry/metabolism ; Ubiquitination
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  • 155
    Publikationsdatum: 2012-03-10
    Beschreibung: Amyloid diseases, including Alzheimer's, Parkinson's, and the prion conditions, are each associated with a particular protein in fibrillar form. These amyloid fibrils were long suspected to be the disease agents, but evidence suggests that smaller, often transient and polymorphic oligomers are the toxic entities. Here, we identify a segment of the amyloid-forming protein alphaB crystallin, which forms an oligomeric complex exhibiting properties of other amyloid oligomers: beta-sheet-rich structure, cytotoxicity, and recognition by an oligomer-specific antibody. The x-ray-derived atomic structure of the oligomer reveals a cylindrical barrel, formed from six antiparallel protein strands, that we term a cylindrin. The cylindrin structure is compatible with a sequence segment from the beta-amyloid protein of Alzheimer's disease. Cylindrins offer models for the hitherto elusive structures of amyloid oligomers.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3959867/" 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/PMC3959867/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Laganowsky, Arthur -- Liu, Cong -- Sawaya, Michael R -- Whitelegge, Julian P -- Park, Jiyong -- Zhao, Minglei -- Pensalfini, Anna -- Soriaga, Angela B -- Landau, Meytal -- Teng, Poh K -- Cascio, Duilio -- Glabe, Charles -- Eisenberg, David -- 016570/PHS HHS/ -- 1R01-AG029430/AG/NIA NIH HHS/ -- 5T32GM008496/GM/NIGMS NIH HHS/ -- P50 AG016570/AG/NIA NIH HHS/ -- R01 AG029430/AG/NIA NIH HHS/ -- R01 AG033069/AG/NIA NIH HHS/ -- RR-15301/RR/NCRR NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2012 Mar 9;335(6073):1228-31. doi: 10.1126/science.1213151.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biological Chemistry, University of California Los Angeles (UCLA), Howard Hughes Medical Institute (HHMI), Los Angeles, CA 90095, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22403391" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Amino Acid Sequence ; Amyloid/*chemistry/immunology ; Amyloid beta-Peptides/chemistry ; Antibodies/immunology ; Crystallography, X-Ray ; Hydrogen Bonding ; Models, Molecular ; Molecular Dynamics Simulation ; Molecular Sequence Data ; Peptide Fragments/*chemistry/immunology ; Protein Conformation ; Protein Structure, Tertiary ; Recombinant Proteins/chemistry ; alpha-Crystallin B Chain/*chemistry/immunology
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  • 156
    facet.materialart.
    Unbekannt
    American Association for the Advancement of Science (AAAS)
    Publikationsdatum: 2012-01-28
    Beschreibung: Two-pore domain potassium (K(+)) channels (K2P channels) control the negative resting potential of eukaryotic cells and regulate cell excitability by conducting K(+) ions across the plasma membrane. Here, we present the 3.4 angstrom resolution crystal structure of a human K2P channel, K2P1 (TWIK-1). Unlike other K(+) channel structures, K2P1 is dimeric. An extracellular cap domain located above the selectivity filter forms an ion pathway in which K(+) ions flow through side portals. Openings within the transmembrane region expose the pore to the lipid bilayer and are filled with electron density attributable to alkyl chains. An interfacial helix appears structurally poised to affect gating. The structure lays a foundation to further investigate how K2P channels are regulated by diverse stimuli.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Miller, Alexandria N -- Long, Stephen B -- New York, N.Y. -- Science. 2012 Jan 27;335(6067):432-6. doi: 10.1126/science.1213274.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Structural Biology Program, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22282804" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Amino Acid Sequence ; Cell Membrane/chemistry ; Crystallization ; Crystallography, X-Ray ; Humans ; Ion Channel Gating ; Lipid Bilayers/chemistry ; Membrane Potentials ; Models, Molecular ; Molecular Sequence Data ; Potassium/metabolism ; Potassium Channels, Tandem Pore Domain/*chemistry/metabolism ; Protein Conformation ; Protein Multimerization ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Recombinant Proteins/chemistry
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  • 157
    facet.materialart.
    Unbekannt
    American Association for the Advancement of Science (AAAS)
    Publikationsdatum: 2012-06-02
    Beschreibung: Designing protein molecules that will assemble into various kinds of ordered materials represents an important challenge in nanotechnology. We report the crystal structure of a 12-subunit protein cage that self-assembles by design to form a tetrahedral structure roughly 16 nanometers in diameter. The strategy of fusing together oligomeric protein domains can be generalized to produce other kinds of cages or extended materials.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lai, Yen-Ting -- Cascio, Duilio -- Yeates, Todd O -- New York, N.Y. -- Science. 2012 Jun 1;336(6085):1129. doi: 10.1126/science.1219351.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉University of California Los Angeles Biomedical Engineering Interdepartmental Program, Los Angeles, CA 90095, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22654051" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Crystallography, X-Ray ; Models, Molecular ; Peroxidases/*chemistry ; Protein Conformation ; *Protein Engineering ; Protein Multimerization ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Protein Subunits/chemistry ; Proteins/*chemistry ; Viral Matrix Proteins/*chemistry
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  • 158
    Publikationsdatum: 2012-11-28
    Beschreibung: Influenza virus ribonucleoprotein complexes (RNPs) are central to the viral life cycle and in adaptation to new host species. RNPs are composed of the viral genome, viral polymerase, and many copies of the viral nucleoprotein. In vitro cell expression of all RNP protein components with four of the eight influenza virus gene segments enabled structural determination of native influenza virus RNPs by means of cryogenic electron microscopy (cryo-EM). The cryo-EM structure reveals the architecture and organization of the native RNP, defining the attributes of its largely helical structure and how polymerase interacts with nucleoprotein and the viral genome. Observations of branched-RNP structures in negative-stain electron microscopy and their putative identification as replication intermediates suggest a mechanism for viral replication by a second polymerase on the RNP template.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3578580/" 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/PMC3578580/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Moeller, Arne -- Kirchdoerfer, Robert N -- Potter, Clinton S -- Carragher, Bridget -- Wilson, Ian A -- 2P41RR017573-11/RR/NCRR NIH HHS/ -- 9 P41 GM103310-11/GM/NIGMS NIH HHS/ -- AI058113/AI/NIAID NIH HHS/ -- GM095573/GM/NIGMS NIH HHS/ -- P01 AI058113/AI/NIAID NIH HHS/ -- P41 GM103310/GM/NIGMS NIH HHS/ -- P50GM073197/GM/NIGMS NIH HHS/ -- R01 GM095573/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2012 Dec 21;338(6114):1631-4. doi: 10.1126/science.1227270. Epub 2012 Nov 22.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉National Resource for Automated Molecular Microscopy, Department of Cell Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23180774" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Cryoelectron Microscopy ; Crystallography, X-Ray ; Genome, Viral ; Image Processing, Computer-Assisted ; Influenza A Virus, H1N1 Subtype/*chemistry/genetics/physiology/*ultrastructure ; Microscopy, Electron ; Models, Molecular ; Nucleic Acid Conformation ; Protein Conformation ; Protein Subunits/chemistry/metabolism ; RNA Replicase/*chemistry/metabolism/ultrastructure ; RNA, Viral/*chemistry/metabolism/ultrastructure ; RNA-Binding Proteins/chemistry/metabolism/ultrastructure ; Ribonucleoproteins/*chemistry/genetics/metabolism/ultrastructure ; Transcription, Genetic ; Viral Core Proteins/chemistry/metabolism/ultrastructure ; Viral Proteins/*chemistry/metabolism/ultrastructure ; *Virus Replication
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  • 159
    facet.materialart.
    Unbekannt
    American Association for the Advancement of Science (AAAS)
    Publikationsdatum: 2012-04-28
    Beschreibung: Argonaute proteins form the functional core of the RNA-induced silencing complexes that mediate RNA silencing in eukaryotes. The 2.3 angstrom resolution crystal structure of human Argonaute2 (Ago2) reveals a bilobed molecule with a central cleft for binding guide and target RNAs. Nucleotides 2 to 6 of a heterogeneous mixture of guide RNAs are positioned in an A-form conformation for base pairing with target messenger RNAs. Between nucleotides 6 and 7, there is a kink that may function in microRNA target recognition or release of sliced RNA products. Tandem tryptophan-binding pockets in the PIWI domain define a likely interaction surface for recruitment of glycine-tryptophan-182 (GW182) or other tryptophan-rich cofactors. These results will enable structure-based approaches for harnessing the untapped therapeutic potential of RNA silencing in humans.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3521581/" 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/PMC3521581/" 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 -- MacRae, Ian J -- R01 GM086701/GM/NIGMS NIH HHS/ -- U54 GM074898/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2012 May 25;336(6084):1037-40. doi: 10.1126/science.1221551. Epub 2012 Apr 26.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22539551" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Amino Acid Sequence ; Argonaute Proteins/*chemistry/metabolism ; Base Pairing ; Binding Sites ; Crystallography, X-Ray ; Humans ; Hydrogen Bonding ; Hydrophobic and Hydrophilic Interactions ; MicroRNAs/chemistry/metabolism ; Models, Molecular ; Molecular Sequence Data ; Nucleic Acid Conformation ; Protein Conformation ; Protein Structure, Tertiary ; RNA Interference ; RNA, Guide/chemistry/metabolism ; RNA, Messenger/chemistry/metabolism ; Tryptophan/chemistry
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 160
    Publikationsdatum: 2012-08-04
    Beschreibung: Using single-molecule fluorescence resonance energy transfer, we have defined bacterial RNA polymerase (RNAP) clamp conformation at each step in transcription initiation and elongation. We find that the clamp predominantly is open in free RNAP and early intermediates in transcription initiation but closes upon formation of a catalytically competent transcription initiation complex and remains closed during initial transcription and transcription elongation. We show that four RNAP inhibitors interfere with clamp opening. We propose that clamp opening allows DNA to be loaded into and unwound in the RNAP active-center cleft, that DNA loading and unwinding trigger clamp closure, and that clamp closure accounts for the high stability of initiation complexes and the high stability and processivity of elongation complexes.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3626110/" 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/PMC3626110/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chakraborty, Anirban -- Wang, Dongye -- Ebright, Yon W -- Korlann, You -- Kortkhonjia, Ekaterine -- Kim, Taiho -- Chowdhury, Saikat -- Wigneshweraraj, Sivaramesh -- Irschik, Herbert -- Jansen, Rolf -- Nixon, B Tracy -- Knight, Jennifer -- Weiss, Shimon -- Ebright, Richard H -- AI072766/AI/NIAID NIH HHS/ -- BB/E023703/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- GM037554/GM/NIGMS NIH HHS/ -- GM069709/GM/NIGMS NIH HHS/ -- GM069937/GM/NIGMS NIH HHS/ -- GM41376/GM/NIGMS NIH HHS/ -- R01 AI072766/AI/NIAID NIH HHS/ -- R01 GM041376/GM/NIGMS NIH HHS/ -- R01 GM069709/GM/NIGMS NIH HHS/ -- R37 GM041376/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2012 Aug 3;337(6094):591-5. doi: 10.1126/science.1218716.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Waksman Institute, and Department of Chemistry and Chemical Biology, Rutgers University, Piscataway, NJ 08854, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22859489" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): DNA Polymerase III/*chemistry/drug effects ; Fluorescence Resonance Energy Transfer/methods ; *Gene Expression Regulation, Bacterial ; Protein Conformation ; *Transcription, Genetic
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  • 161
    Publikationsdatum: 2012-07-17
    Beschreibung: Pharmacological responses of G protein-coupled receptors (GPCRs) can be fine-tuned by allosteric modulators. Structural studies of such effects have been limited due to the medium resolution of GPCR structures. We reengineered the human A(2A) adenosine receptor by replacing its third intracellular loop with apocytochrome b(562)RIL and solved the structure at 1.8 angstrom resolution. The high-resolution structure allowed us to identify 57 ordered water molecules inside the receptor comprising three major clusters. The central cluster harbors a putative sodium ion bound to the highly conserved aspartate residue Asp(2.50). Additionally, two cholesterols stabilize the conformation of helix VI, and one of 23 ordered lipids intercalates inside the ligand-binding pocket. These high-resolution details shed light on the potential role of structured water molecules, sodium ions, and lipids/cholesterol in GPCR stabilization and function.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3399762/" 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/PMC3399762/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Liu, Wei -- Chun, Eugene -- Thompson, Aaron A -- Chubukov, Pavel -- Xu, Fei -- Katritch, Vsevolod -- Han, Gye Won -- Roth, Christopher B -- Heitman, Laura H -- IJzerman, Adriaan P -- Cherezov, Vadim -- Stevens, Raymond C -- P50 GM073197/GM/NIGMS NIH HHS/ -- R01 GM089857/GM/NIGMS 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. 2012 Jul 13;337(6091):232-6. doi: 10.1126/science.1219218.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular 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/22798613" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Adenosine A2 Receptor Agonists/metabolism ; Adenosine A2 Receptor Antagonists/metabolism ; Allosteric Regulation ; Cholesterol/chemistry ; Crystallography, X-Ray ; Cytochrome b Group/chemistry ; Escherichia coli Proteins/chemistry ; HEK293 Cells ; Humans ; Hydrogen Bonding ; Ligands ; Lipid Bilayers ; Lipids/chemistry ; Models, Molecular ; Protein Conformation ; Protein Engineering ; Protein Structure, Secondary ; Receptor, Adenosine A2A/*chemistry/*metabolism ; Recombinant Fusion Proteins/chemistry/metabolism ; Sodium/*analysis ; Triazines/metabolism ; Triazoles/metabolism ; Water/chemistry
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  • 162
    Publikationsdatum: 2012-01-24
    Beschreibung: Tethering a single lysozyme molecule to a carbon nanotube field-effect transistor produced a stable, high-bandwidth transducer for protein motion. Electronic monitoring during 10-minute periods extended well beyond the limitations of fluorescence techniques to uncover dynamic disorder within a single molecule and establish lysozyme as a processive enzyme. On average, 100 chemical bonds are processively hydrolyzed, at 15-hertz rates, before lysozyme returns to its nonproductive, 330-hertz hinge motion. Statistical analysis differentiated single-step hinge closure from enzyme opening, which requires two steps. Seven independent time scales governing lysozyme's activity were observed. The pH dependence of lysozyme activity arises not from changes to its processive kinetics but rather from increasing time spent in either nonproductive rapid motions or an inactive, closed conformation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3914775/" 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/PMC3914775/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Choi, Yongki -- Moody, Issa S -- Sims, Patrick C -- Hunt, Steven R -- Corso, Brad L -- Perez, Israel -- Weiss, Gregory A -- Collins, Philip G -- R01 CA133592/CA/NCI NIH HHS/ -- R01 CA133592-01/CA/NCI NIH HHS/ -- T32 CA009054/CA/NCI NIH HHS/ -- T32CA009054/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2012 Jan 20;335(6066):319-24. doi: 10.1126/science.1214824.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute for Surface and Interface Science, University of California Irvine, Irvine, CA 92697-2375, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22267809" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Bacteriophage T4/enzymology ; Biocatalysis ; Electric Conductivity ; Fluorescence Resonance Energy Transfer ; Hydrogen-Ion Concentration ; Kinetics ; Microscopy, Atomic Force ; Muramidase/*chemistry/*metabolism ; Nanotubes, Carbon ; Peptidoglycan/metabolism ; Protein Conformation ; Pyrenes ; Static Electricity ; Thermodynamics ; Transistors, Electronic
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  • 163
    Publikationsdatum: 2012-04-21
    Beschreibung: Studying solvation of a large molecule on an atomic level is challenging because of the transient character and inhomogeneity of hydrogen bonding in liquid water. We studied water clusters of a protonated macrocyclic decapeptide, gramicidin S, which were prepared in the gas phase and then cooled to cryogenic temperatures. The experiment spectroscopically tracked fine structural changes of the clusters upon increasing the number of attached water molecules from 1 to 50 and distinguished vibrational fingerprints of different conformers. The data indicate that only the first two water molecules induce a substantial change of the gramicidin S structure by breaking two intramolecular noncovalent bonds. The peptide structure remains largely intact upon further solvation, reflecting the interplay between the strong intramolecular and weaker intermolecular hydrogen bonds.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nagornova, Natalia S -- Rizzo, Thomas R -- Boyarkin, Oleg V -- New York, N.Y. -- Science. 2012 Apr 20;336(6079):320-3. doi: 10.1126/science.1218709.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratoire de Chimie Physique Moleculaire, Ecole Polytechnique Federale de Lausanne, CH-1015 Lausanne, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22517854" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Binding Sites ; Gramicidin/*chemistry ; Hydrogen Bonding ; Nuclear Magnetic Resonance, Biomolecular ; Physicochemical Processes ; Protein Conformation ; Solubility ; Spectrophotometry, Infrared ; Spectrophotometry, Ultraviolet ; Water/chemistry
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  • 164
    facet.materialart.
    Unbekannt
    American Association for the Advancement of Science (AAAS)
    Publikationsdatum: 2012-10-09
    Beschreibung: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Service, Robert F -- New York, N.Y. -- Science. 2012 Oct 5;338(6103):28. doi: 10.1126/science.338.6103.28.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23042861" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Biological Products/*chemical synthesis/chemistry ; Carbohydrates/chemistry ; *Chemistry Techniques, Synthetic ; Erythropoietin/*chemical synthesis/chemistry ; Pharmaceutical Preparations/*chemical synthesis ; Protein Conformation
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  • 165
    Publikationsdatum: 2012-02-22
    Beschreibung: Toll-like receptor 5 (TLR5) binding to bacterial flagellin activates signaling through the transcription factor NF-kappaB and triggers an innate immune response to the invading pathogen. To elucidate the structural basis and mechanistic implications of TLR5-flagellin recognition, we determined the crystal structure of zebrafish TLR5 (as a variable lymphocyte receptor hybrid protein) in complex with the D1/D2/D3 fragment of Salmonella flagellin, FliC, at 2.47 angstrom resolution. TLR5 interacts primarily with the three helices of the FliC D1 domain using its lateral side. Two TLR5-FliC 1:1 heterodimers assemble into a 2:2 tail-to-tail signaling complex that is stabilized by quaternary contacts of the FliC D1 domain with the convex surface of the opposing TLR5. The proposed signaling mechanism is supported by structure-guided mutagenesis and deletion analyses on CBLB502, a therapeutic protein derived from FliC.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3406927/" 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/PMC3406927/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yoon, Sung-il -- Kurnasov, Oleg -- Natarajan, Venkatesh -- Hong, Minsun -- Gudkov, Andrei V -- Osterman, Andrei L -- Wilson, Ian A -- AI042266/AI/NIAID NIH HHS/ -- R01 AI042266/AI/NIAID NIH HHS/ -- R01 AI042266-05/AI/NIAID NIH HHS/ -- R01 AI080446/AI/NIAID NIH HHS/ -- R01 AI080446-05/AI/NIAID NIH HHS/ -- RC2 AI087616/AI/NIAID NIH HHS/ -- RC2 AI087616-02/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2012 Feb 17;335(6070):859-64. doi: 10.1126/science.1215584.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22344444" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Animals ; Crystallography, X-Ray ; Dimerization ; Flagellin/*chemistry/metabolism ; Models, Molecular ; Mutagenesis ; Protein Conformation ; Salmonella enterica ; *Signal Transduction ; Structure-Activity Relationship ; Toll-Like Receptor 5/*chemistry/genetics/metabolism ; Zebrafish ; Zebrafish Proteins/*chemistry/genetics/metabolism
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  • 166
    facet.materialart.
    Unbekannt
    American Association for the Advancement of Science (AAAS)
    Publikationsdatum: 2012-03-03
    Beschreibung: Enterovirus 71 is a picornavirus associated with fatal neurological illness in infants and young children. Here, we report the crystal structure of enterovirus 71 and show that, unlike in other enteroviruses, the "pocket factor," a small molecule that stabilizes the virus, is partly exposed on the floor of the "canyon." Thus, the structure of antiviral compounds may require a hydrophilic head group designed to interact with residues at the entrance of the pocket.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3448362/" 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/PMC3448362/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Plevka, Pavel -- Perera, Rushika -- Cardosa, Jane -- Kuhn, Richard J -- Rossmann, Michael G -- AI11219/AI/NIAID NIH HHS/ -- R37 AI011219/AI/NIAID NIH HHS/ -- RR007707/RR/NCRR NIH HHS/ -- New York, N.Y. -- Science. 2012 Jun 8;336(6086):1274. doi: 10.1126/science.1218713. Epub 2012 Mar 1.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biological Sciences, Purdue University, West Lafayette, IN 47907, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22383808" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Capsid/chemistry/metabolism/ultrastructure ; Capsid Proteins/*chemistry/metabolism ; Crystallography, X-Ray ; Enterovirus A, Human/*chemistry/metabolism/*ultrastructure ; Humans ; Hydrophobic and Hydrophilic Interactions ; Models, Molecular ; Protein Conformation ; Receptors, Virus/metabolism
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  • 167
    facet.materialart.
    Unbekannt
    American Association for the Advancement of Science (AAAS)
    Publikationsdatum: 2012-05-19
    Beschreibung: Eubacteria inactivate their ribosomes as 100S dimers or 70S monomers upon entry into stationary phase. In Escherichia coli, 100S dimer formation is mediated by ribosome modulation factor (RMF) and hibernation promoting factor (HPF), or alternatively, the YfiA protein inactivates ribosomes as 70S monomers. Here, we present high-resolution crystal structures of the Thermus thermophilus 70S ribosome in complex with each of these stationary-phase factors. The binding site of RMF overlaps with that of the messenger RNA (mRNA) Shine-Dalgarno sequence, which prevents the interaction between the mRNA and the 16S ribosomal RNA. The nearly identical binding sites of HPF and YfiA overlap with those of the mRNA, transfer RNA, and initiation factors, which prevents translation initiation. The binding of RMF and HPF, but not YfiA, to the ribosome induces a conformational change of the 30S head domain that promotes 100S dimer formation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3377384/" 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/PMC3377384/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Polikanov, Yury S -- Blaha, Gregor M -- Steitz, Thomas A -- GM022778/GM/NIGMS NIH HHS/ -- P01 GM022778/GM/NIGMS NIH HHS/ -- P30 EB009998/EB/NIBIB NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2012 May 18;336(6083):915-8. doi: 10.1126/science.1218538.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520-8114, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22605777" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Bacterial Proteins/*biosynthesis ; Binding Sites ; Crystallography, X-Ray ; Escherichia coli Proteins/*chemistry/metabolism ; Models, Molecular ; Peptide Chain Initiation, Translational ; Prokaryotic Initiation Factors/metabolism ; Protein Binding ; Protein Conformation ; Protein Structure, Tertiary ; RNA, Bacterial/chemistry/metabolism ; RNA, Messenger/chemistry/metabolism ; RNA, Ribosomal, 16S/chemistry/metabolism ; RNA, Transfer/chemistry/metabolism ; Ribosomal Proteins/*chemistry/metabolism ; Ribosome Subunits, Small, Bacterial/chemistry/metabolism/ultrastructure ; Ribosomes/*chemistry/metabolism/ultrastructure ; Thermus thermophilus/*chemistry
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  • 168
    Publikationsdatum: 2013-11-10
    Beschreibung: The last step in eukaryotic translational initiation involves the joining of the large and small subunits of the ribosome, with initiator transfer RNA (Met-tRNA(i)(Met)) positioned over the start codon of messenger RNA in the P site. This step is catalyzed by initiation factor eIF5B. We used recent advances in cryo-electron microscopy (cryo-EM) to determine a structure of the eIF5B initiation complex to 6.6 angstrom resolution from 〈3% of the population, comprising just 5143 particles. The structure reveals conformational changes in eIF5B, initiator tRNA, and the ribosome that provide insights into the role of eIF5B in translational initiation. The relatively high resolution obtained from such a small fraction of a heterogeneous sample suggests a general approach for characterizing the structure of other dynamic or transient biological complexes.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3836175/" 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/PMC3836175/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fernandez, Israel S -- Bai, Xiao-Chen -- Hussain, Tanweer -- Kelley, Ann C -- Lorsch, Jon R -- Ramakrishnan, V -- Scheres, Sjors H W -- 096570/Wellcome Trust/United Kingdom -- MC_U105184332/Medical Research Council/United Kingdom -- MC_UP_A025_1013/Medical Research Council/United Kingdom -- WT096570/Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2013 Nov 15;342(6160):1240585. doi: 10.1126/science.1240585. Epub 2013 Nov 7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉MRC Laboratory of Molecular Biology, Cambridge Biomedical Campus, Cambridge CB2 0QH, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24200810" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Analytic Sample Preparation Methods ; Cryoelectron Microscopy/methods ; Eukaryotic Initiation Factors/*chemistry ; Humans ; *Peptide Chain Initiation, Translational ; Protein Conformation ; RNA, Transfer, Met/chemistry ; Ribosomes/*chemistry ; Saccharomyces cerevisiae
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  • 169
    Publikationsdatum: 2012-10-23
    Beschreibung: During transcription initiation, RNA polymerase (RNAP) binds and unwinds promoter DNA to form an RNAP-promoter open complex. We have determined crystal structures at 2.9 and 3.0 A resolution of functional transcription initiation complexes comprising Thermus thermophilus RNA polymerase, sigma(A), and a promoter DNA fragment corresponding to the transcription bubble and downstream double-stranded DNA of the RNAP-promoter open complex. The structures show that sigma recognizes the -10 element and discriminator element through interactions that include the unstacking and insertion into pockets of three DNA bases and that RNAP recognizes the -4/+2 region through interactions that include the unstacking and insertion into a pocket of the +2 base. The structures further show that interactions between sigma and template-strand single-stranded DNA (ssDNA) preorganize template-strand ssDNA to engage the RNAP active center.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3593053/" 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/PMC3593053/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhang, Yu -- Feng, Yu -- Chatterjee, Sujoy -- Tuske, Steve -- Ho, Mary X -- Arnold, Eddy -- Ebright, Richard H -- AI072766/AI/NIAID NIH HHS/ -- GM41376/GM/NIGMS NIH HHS/ -- P30 EB009998/EB/NIBIB NIH HHS/ -- R01 AI072766/AI/NIAID NIH HHS/ -- R01 GM041376/GM/NIGMS NIH HHS/ -- R37 GM041376/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2012 Nov 23;338(6110):1076-80. doi: 10.1126/science.1227786. Epub 2012 Oct 18.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Waksman Institute, and Department of Chemistry and Chemical Biology, Rutgers University, Piscataway, NJ 08854, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23086998" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Crystallography, X-Ray ; DNA, Single-Stranded/chemistry ; DNA-Directed RNA Polymerases/*chemistry ; *Gene Expression Regulation, Bacterial ; Promoter Regions, Genetic ; Protein Conformation ; Sigma Factor/*chemistry ; Thermus thermophilus/*enzymology/*genetics ; *Transcription Initiation, Genetic
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  • 170
    Publikationsdatum: 2012-11-10
    Beschreibung: Fluorescent proteins (FPs) are widely used as optical sensors, whereas other light-absorbing domains have been used for optical control of protein localization or activity. Here, we describe light-dependent dissociation and association in a mutant of the photochromic FP Dronpa, and we used it to control protein activities with light. We created a fluorescent light-inducible protein design in which Dronpa domains are fused to both termini of an enzyme domain. In the dark, the Dronpa domains associate and cage the protein, but light induces Dronpa dissociation and activates the protein. This method enabled optical control over guanine nucleotide exchange factor and protease domains without extensive screening. Our findings extend the applications of FPs from exclusively sensing functions to also encompass optogenetic control.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3702057/" 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/PMC3702057/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhou, Xin X -- Chung, Hokyung K -- Lam, Amy J -- Lin, Michael Z -- R01 NS076860/NS/NINDS NIH HHS/ -- R01NS076860/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2012 Nov 9;338(6108):810-4. doi: 10.1126/science.1226854.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Bioengineering, Stanford University, Stanford, CA 94305, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23139335" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Adaptor Proteins, Vesicular Transport/chemistry/genetics/metabolism ; Animals ; Cell Membrane/metabolism ; Darkness ; Fluorescence ; HeLa Cells ; Humans ; *Light ; Luminescent Proteins/*chemistry/genetics/metabolism ; Mice ; Models, Molecular ; NIH 3T3 Cells ; Native Polyacrylamide Gel Electrophoresis ; Optogenetics ; Protein Conformation ; Protein Engineering ; Protein Multimerization ; *Protein Structure, Tertiary ; Pseudopodia/metabolism/ultrastructure ; Recombinant Fusion Proteins/*chemistry/genetics/metabolism ; Serine Endopeptidases/chemistry/genetics/metabolism ; Viral Nonstructural Proteins/chemistry/genetics/metabolism
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 171
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    American Association for the Advancement of Science (AAAS)
    Publikationsdatum: 2012-06-23
    Beschreibung: 〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3942086/" 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/PMC3942086/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Prusiner, Stanley B -- P01 AG002132/AG/NIA NIH HHS/ -- P01 AG010770/AG/NIA NIH HHS/ -- P01 AG021601/AG/NIA NIH HHS/ -- New York, N.Y. -- Science. 2012 Jun 22;336(6088):1511-3. doi: 10.1126/science.1222951.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute for Neurodegenerative Diseases and Department of Neurology, University of California, San Francisco, San Francisco, CA 94143, USA. stanley@ind.ucsf.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22723400" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Animals ; Fungal Proteins/chemistry/metabolism ; Humans ; Neurodegenerative Diseases/*etiology/*metabolism ; Prion Diseases/*etiology/metabolism ; Prions/*chemistry/metabolism/*pathogenicity ; Protein Conformation
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  • 172
    Publikationsdatum: 2012-11-03
    Beschreibung: Ribosomal proteins are synthesized in the cytoplasm, before nuclear import and assembly with ribosomal RNA (rRNA). Little is known about coordination of nucleocytoplasmic transport with ribosome assembly. Here, we identify a transport adaptor, symportin 1 (Syo1), that facilitates synchronized coimport of the two 5S-rRNA binding proteins Rpl5 and Rpl11. In vitro studies revealed that Syo1 concomitantly binds Rpl5-Rpl11 and furthermore recruits the import receptor Kap104. The Syo1-Rpl5-Rpl11 import complex is released from Kap104 by RanGTP and can be directly transferred onto the 5S rRNA. Syo1 can shuttle back to the cytoplasm by interaction with phenylalanine-glycine nucleoporins. X-ray crystallography uncovered how the alpha-solenoid symportin accommodates the Rpl5 amino terminus, normally bound to 5S rRNA, in an extended groove. Symportin-mediated coimport of Rpl5-Rpl11 could ensure coordinated and stoichiometric incorporation of these proteins into pre-60S ribosomes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kressler, Dieter -- Bange, Gert -- Ogawa, Yutaka -- Stjepanovic, Goran -- Bradatsch, Bettina -- Pratte, Dagmar -- Amlacher, Stefan -- Strauss, Daniela -- Yoneda, Yoshihiro -- Katahira, Jun -- Sinning, Irmgard -- Hurt, Ed -- New York, N.Y. -- Science. 2012 Nov 2;338(6107):666-71. doi: 10.1126/science.1226960.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Biochemie-Zentrum der Universitat Heidelberg, Im Neuenheimer Feld 328, Heidelberg D-69120, Germany. dieter.kressler@unifr.ch〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23118189" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): *Active Transport, Cell Nucleus ; Amino Acid Sequence ; Base Sequence ; Cell Nucleus/*metabolism ; Chaetomium/metabolism ; Crystallography, X-Ray ; Fungal Proteins/chemistry/metabolism ; Models, Molecular ; Molecular Sequence Data ; Protein Binding ; Protein Conformation ; Protein Multimerization ; Protein Structure, Tertiary ; RNA, Fungal/metabolism ; RNA, Ribosomal, 5S/metabolism ; RNA-Binding Proteins/chemistry/*metabolism ; Ribosomal Proteins/chemistry/*metabolism ; Ribosomes/*metabolism ; Saccharomyces cerevisiae/*metabolism ; Saccharomyces cerevisiae Proteins/chemistry/*metabolism ; beta Karyopherins/metabolism
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 173
    Publikationsdatum: 2012-01-10
    Beschreibung: TAL (transcription activator-like) effectors, secreted by phytopathogenic bacteria, recognize host DNA sequences through a central domain of tandem repeats. Each repeat comprises 33 to 35 conserved amino acids and targets a specific base pair by using two hypervariable residues [known as repeat variable diresidues (RVDs)] at positions 12 and 13. Here, we report the crystal structures of an 11.5-repeat TAL effector in both DNA-free and DNA-bound states. Each TAL repeat comprises two helices connected by a short RVD-containing loop. The 11.5 repeats form a right-handed, superhelical structure that tracks along the sense strand of DNA duplex, with RVDs contacting the major groove. The 12th residue stabilizes the RVD loop, whereas the 13th residue makes a base-specific contact. Understanding DNA recognition by TAL effectors may facilitate rational design of DNA-binding proteins with biotechnological applications.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3586824/" 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/PMC3586824/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Deng, Dong -- Yan, Chuangye -- Pan, Xiaojing -- Mahfouz, Magdy -- Wang, Jiawei -- Zhu, Jian-Kang -- Shi, Yigong -- Yan, Nieng -- R01 GM070795/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2012 Feb 10;335(6069):720-3. doi: 10.1126/science.1215670. Epub 2012 Jan 5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉State Key Laboratory of Bio-Membrane and Membrane Biotechnology, Tsinghua University, Beijing 100084, China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22223738" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Amino Acid Sequence ; Bacterial Proteins/*chemistry/*metabolism ; Base Sequence ; Crystallography, X-Ray ; DNA/chemistry/*metabolism ; DNA-Binding Proteins/chemistry/metabolism ; Hydrogen Bonding ; Models, Molecular ; Molecular Sequence Data ; Physicochemical Processes ; Protein Conformation ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Repetitive Sequences, Amino Acid ; Virulence Factors/*chemistry/*metabolism ; Xanthomonas/chemistry/pathogenicity
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 174
    Publikationsdatum: 2013-04-13
    Beschreibung: 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〉
    Schlagwort(e): Circular Dichroism ; Microscopy, Electron, Scanning ; Models, Molecular ; Molecular Dynamics Simulation ; *Nanostructures ; Peptides/*chemistry ; Protein Conformation ; Protein Folding ; Protein Multimerization ; Protein Structure, Secondary ; Thermodynamics
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 175
    Publikationsdatum: 2013-02-16
    Beschreibung: Intense femtosecond x-ray pulses produced at the Linac Coherent Light Source (LCLS) were used for simultaneous x-ray diffraction (XRD) and x-ray emission spectroscopy (XES) of microcrystals of photosystem II (PS II) at room temperature. This method probes the overall protein structure and the electronic structure of the Mn4CaO5 cluster in the oxygen-evolving complex of PS II. XRD data are presented from both the dark state (S1) and the first illuminated state (S2) of PS II. Our simultaneous XRD-XES study shows that the PS II crystals are intact during our measurements at the LCLS, not only with respect to the structure of PS II, but also with regard to the electronic structure of the highly radiation-sensitive Mn4CaO5 cluster, opening new directions for future dynamics studies.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3732582/" 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/PMC3732582/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kern, Jan -- Alonso-Mori, Roberto -- Tran, Rosalie -- Hattne, Johan -- Gildea, Richard J -- Echols, Nathaniel -- Glockner, Carina -- Hellmich, Julia -- Laksmono, Hartawan -- Sierra, Raymond G -- Lassalle-Kaiser, Benedikt -- Koroidov, Sergey -- Lampe, Alyssa -- Han, Guangye -- Gul, Sheraz -- Difiore, Dorte -- Milathianaki, Despina -- Fry, Alan R -- Miahnahri, Alan -- Schafer, Donald W -- Messerschmidt, Marc -- Seibert, M Marvin -- Koglin, Jason E -- Sokaras, Dimosthenis -- Weng, Tsu-Chien -- Sellberg, Jonas -- Latimer, Matthew J -- Grosse-Kunstleve, Ralf W -- Zwart, Petrus H -- White, William E -- Glatzel, Pieter -- Adams, Paul D -- Bogan, Michael J -- Williams, Garth J -- Boutet, Sebastien -- Messinger, Johannes -- Zouni, Athina -- Sauter, Nicholas K -- Yachandra, Vittal K -- Bergmann, Uwe -- Yano, Junko -- GM095887/GM/NIGMS NIH HHS/ -- GM102520/GM/NIGMS NIH HHS/ -- P01 GM063210/GM/NIGMS NIH HHS/ -- P41GM103393/GM/NIGMS NIH HHS/ -- R01 GM055302/GM/NIGMS NIH HHS/ -- R01 GM095887/GM/NIGMS NIH HHS/ -- R01 GM102520/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2013 Apr 26;340(6131):491-5. doi: 10.1126/science.1234273. Epub 2013 Feb 14.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Physical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23413188" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Crystallography, X-Ray/methods ; Cyanobacteria/enzymology ; Electrons ; Light ; Manganese Compounds/*chemistry ; Oxidation-Reduction ; Oxides/*chemistry ; Photosystem II Protein Complex/*chemistry/radiation effects ; Protein Conformation ; Spectrometry, X-Ray Emission/methods ; Temperature ; Water/chemistry ; X-Ray Diffraction/methods
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 176
    Publikationsdatum: 2013-12-21
    Beschreibung: X-ray crystallography of G protein-coupled receptors and other membrane proteins is hampered by difficulties associated with growing sufficiently large crystals that withstand radiation damage and yield high-resolution data at synchrotron sources. We used an x-ray free-electron laser (XFEL) with individual 50-femtosecond-duration x-ray pulses to minimize radiation damage and obtained a high-resolution room-temperature structure of a human serotonin receptor using sub-10-micrometer microcrystals grown in a membrane mimetic matrix known as lipidic cubic phase. Compared with the structure solved by using traditional microcrystallography from cryo-cooled crystals of about two orders of magnitude larger volume, the room-temperature XFEL structure displays a distinct distribution of thermal motions and conformations of residues that likely more accurately represent the receptor structure and dynamics in a cellular environment.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3902108/" 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/PMC3902108/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Liu, Wei -- Wacker, Daniel -- Gati, Cornelius -- Han, Gye Won -- James, Daniel -- Wang, Dingjie -- Nelson, Garrett -- Weierstall, Uwe -- Katritch, Vsevolod -- Barty, Anton -- Zatsepin, Nadia A -- Li, Dianfan -- Messerschmidt, Marc -- Boutet, Sebastien -- Williams, Garth J -- Koglin, Jason E -- Seibert, M Marvin -- Wang, Chong -- Shah, Syed T A -- Basu, Shibom -- Fromme, Raimund -- Kupitz, Christopher -- Rendek, Kimberley N -- Grotjohann, Ingo -- Fromme, Petra -- Kirian, Richard A -- Beyerlein, Kenneth R -- White, Thomas A -- Chapman, Henry N -- Caffrey, Martin -- Spence, John C H -- Stevens, Raymond C -- Cherezov, Vadim -- P50 GM073197/GM/NIGMS NIH HHS/ -- P50 GM073210/GM/NIGMS NIH HHS/ -- R01 GM095583/GM/NIGMS NIH HHS/ -- U54 GM094599/GM/NIGMS NIH HHS/ -- U54 GM094618/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2013 Dec 20;342(6165):1521-4. doi: 10.1126/science.1244142.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24357322" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Crystallography, X-Ray/*instrumentation/*methods ; Humans ; Lasers ; Protein Conformation ; Receptor, Serotonin, 5-HT2B/chemistry/radiation effects ; Receptors, G-Protein-Coupled/*chemistry/radiation effects ; Time Factors
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 177
    facet.materialart.
    Unbekannt
    American Association for the Advancement of Science (AAAS)
    Publikationsdatum: 2013-01-26
    Beschreibung: 〈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〉
    Schlagwort(e): 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
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 178
    Publikationsdatum: 2013-08-24
    Beschreibung: Many studies have implicated a role for conformational motions during the catalytic cycle, acting to optimize the binding pocket or facilitate product release, but a more intimate role in the chemical reaction has not been described. We address this by monitoring active-site loop motion in two protein tyrosine phosphatases (PTPs) using nuclear magnetic resonance spectroscopy. The PTPs, YopH and PTP1B, have very different catalytic rates; however, we find in both that the active-site loop closes to its catalytically competent position at rates that mirror the phosphotyrosine cleavage kinetics. This loop contains the catalytic acid, suggesting that loop closure occurs concomitantly with the protonation of the leaving group tyrosine and explains the different kinetics of two otherwise chemically and mechanistically indistinguishable enzymes.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4078984/" 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/PMC4078984/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Whittier, Sean K -- Hengge, Alvan C -- Loria, J Patrick -- GM47297/GM/NIGMS NIH HHS/ -- T32 GM008283/GM/NIGMS NIH HHS/ -- T32GM008283/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2013 Aug 23;341(6148):899-903. doi: 10.1126/science.1241735.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biophysics and Biochemistry, Yale University, 260 Whitney Avenue, New Haven, CT 06520, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23970698" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Bacterial Outer Membrane Proteins/*chemistry ; Catalysis ; Catalytic Domain ; Humans ; Motion ; Nuclear Magnetic Resonance, Biomolecular ; Phosphates/*chemistry ; Protein Conformation ; Protein Tyrosine Phosphatase, Non-Receptor Type 1/*chemistry ; Protein Tyrosine Phosphatases/*chemistry ; Vanadates/chemistry
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 179
    Publikationsdatum: 2013-03-23
    Beschreibung: Drugs active at G protein-coupled receptors (GPCRs) can differentially modulate either canonical or noncanonical signaling pathways via a phenomenon known as functional selectivity or biased signaling. We report biochemical studies showing that the hallucinogen lysergic acid diethylamide, its precursor ergotamine (ERG), and related ergolines display strong functional selectivity for beta-arrestin signaling at the 5-HT2B 5-hydroxytryptamine (5-HT) receptor, whereas they are relatively unbiased at the 5-HT1B receptor. To investigate the structural basis for biased signaling, we determined the crystal structure of the human 5-HT2B receptor bound to ERG and compared it with the 5-HT1B/ERG structure. Given the relatively poor understanding of GPCR structure and function to date, insight into different GPCR signaling pathways is important to better understand both adverse and favorable therapeutic activities.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3644390/" 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/PMC3644390/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wacker, Daniel -- Wang, Chong -- Katritch, Vsevolod -- Han, Gye Won -- Huang, Xi-Ping -- Vardy, Eyal -- McCorvy, John D -- Jiang, Yi -- Chu, Meihua -- Siu, Fai Yiu -- Liu, Wei -- Xu, H Eric -- Cherezov, Vadim -- Roth, Bryan L -- Stevens, Raymond C -- P50 GM073197/GM/NIGMS 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):615-9. doi: 10.1126/science.1232808. 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/23519215" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Amino Acid Motifs ; Amino Acid Sequence ; Arrestin/metabolism ; Arrestins/metabolism ; Binding Sites ; Crystallography, X-Ray ; Ergolines/chemistry/metabolism ; Ergotamine/chemistry/*metabolism ; HEK293 Cells ; Humans ; Ligands ; Lysergic Acid Diethylamide/chemistry/metabolism ; Models, Molecular ; Molecular Sequence Data ; Protein Conformation ; Protein Structure, Secondary ; Receptor, Serotonin, 5-HT1B/chemistry/*metabolism ; Receptor, Serotonin, 5-HT2B/*chemistry/*metabolism ; Receptors, Serotonin/chemistry/metabolism ; Signal Transduction
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 180
    facet.materialart.
    Unbekannt
    American Association for the Advancement of Science (AAAS)
    Publikationsdatum: 2013-09-14
    Beschreibung: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cohen, Jon -- New York, N.Y. -- Science. 2013 Sep 13;341(6151):1168-71. doi: 10.1126/science.341.6151.1168.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24030996" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): *AIDS Vaccines ; Acquired Immunodeficiency Syndrome/*immunology/*prevention & control ; HIV Antibodies/*chemistry/*immunology ; HIV Envelope Protein gp120/chemistry/immunology ; HIV Envelope Protein gp41/chemistry/immunology ; Humans ; Models, Chemical ; Protein Conformation
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    Digitale ISSN: 1095-9203
    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 181
    facet.materialart.
    Unbekannt
    American Association for the Advancement of Science (AAAS)
    Publikationsdatum: 2013-08-03
    Beschreibung: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cohen, Jon -- New York, N.Y. -- Science. 2013 Aug 2;341(6145):443-4. doi: 10.1126/science.341.6145.443.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23908196" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): *Artifacts ; Cryoelectron Microscopy/*methods ; HIV/immunology/*ultrastructure ; HIV Envelope Protein gp120/*chemistry/immunology ; HIV Envelope Protein gp41/*chemistry/immunology ; Humans ; Immune System/virology ; Protein Conformation ; Protein Multimerization
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 182
    Publikationsdatum: 2013-02-23
    Beschreibung: Influenza antiviral agents play important roles in modulating disease severity and in controlling pandemics while vaccines are prepared, but the development of resistance to agents like the commonly used neuraminidase inhibitor oseltamivir may limit their future utility. We report here on a new class of specific, mechanism-based anti-influenza drugs that function through the formation of a stabilized covalent intermediate in the influenza neuraminidase enzyme, and we confirm this mode of action with structural and mechanistic studies. These compounds function in cell-based assays and in animal models, with efficacies comparable to that of the neuraminidase inhibitor zanamivir and with broad-spectrum activity against drug-resistant strains in vitro. The similarity of their structure to that of the natural substrate and their mechanism-based design make these attractive antiviral candidates.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kim, Jin-Hyo -- Resende, Ricardo -- Wennekes, Tom -- Chen, Hong-Ming -- Bance, Nicole -- Buchini, Sabrina -- Watts, Andrew G -- Pilling, Pat -- Streltsov, Victor A -- Petric, Martin -- Liggins, Richard -- Barrett, Susan -- McKimm-Breschkin, Jennifer L -- Niikura, Masahiro -- Withers, Stephen G -- G0600514/Medical Research Council/United Kingdom -- Canadian Institutes of Health Research/Canada -- New York, N.Y. -- Science. 2013 Apr 5;340(6128):71-5. doi: 10.1126/science.1232552. Epub 2013 Feb 21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry, University of British Columbia, 2036 Main Mall, Vancouver, British Columbia V6T 1Z1, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23429702" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Animals ; Antiviral Agents/*chemistry/pharmacology ; Crystallography, X-Ray ; Dogs ; Enzyme Inhibitors/*chemistry/pharmacology ; Humans ; Madin Darby Canine Kidney Cells ; Neuraminidase/*antagonists & inhibitors/chemistry ; Orthomyxoviridae/*drug effects/enzymology ; Oseltamivir/chemistry/pharmacology ; Protein Conformation ; Sialic Acids/*chemistry/pharmacology ; Structure-Activity Relationship ; Zanamivir/chemistry/pharmacology
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 183
    Publikationsdatum: 2013-05-11
    Beschreibung: Serum characterization and antibody isolation are transforming our understanding of the humoral immune response to viral infection. Here, we show that epitope specificities of HIV-1-neutralizing antibodies in serum can be elucidated from the serum pattern of neutralization against a diverse panel of HIV-1 isolates. We determined "neutralization fingerprints" for 30 neutralizing antibodies on a panel of 34 diverse HIV-1 strains and showed that similarity in neutralization fingerprint correlated with similarity in epitope. We used these fingerprints to delineate specificities of polyclonal sera from 24 HIV-1-infected donors and a chimeric siman-human immunodeficiency virus-infected macaque. Delineated specificities matched published specificities and were further confirmed by antibody isolation for two sera. Patterns of virus-isolate neutralization can thus afford a detailed epitope-specific understanding of neutralizing-antibody responses to viral infection.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Georgiev, Ivelin S -- Doria-Rose, Nicole A -- Zhou, Tongqing -- Kwon, Young Do -- Staupe, Ryan P -- Moquin, Stephanie -- Chuang, Gwo-Yu -- Louder, Mark K -- Schmidt, Stephen D -- Altae-Tran, Han R -- Bailer, Robert T -- McKee, Krisha -- Nason, Martha -- O'Dell, Sijy -- Ofek, Gilad -- Pancera, Marie -- Srivatsan, Sanjay -- Shapiro, Lawrence -- Connors, Mark -- Migueles, Stephen A -- Morris, Lynn -- Nishimura, Yoshiaki -- Martin, Malcolm A -- Mascola, John R -- Kwong, Peter D -- U19 AI51794/AI/NIAID NIH HHS/ -- Intramural NIH HHS/ -- New York, N.Y. -- Science. 2013 May 10;340(6133):751-6. doi: 10.1126/science.1233989.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23661761" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Animals ; Antibodies, Neutralizing/blood/*immunology ; Epitope Mapping ; HIV Antibodies/blood/*immunology ; HIV Infections/blood/*immunology ; HIV-1/*immunology/isolation & purification ; Humans ; Immunodominant Epitopes/chemistry/immunology ; Macaca ; Neutralization Tests ; Protein Conformation ; Serum/immunology
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 184
    Publikationsdatum: 2013-04-27
    Beschreibung: The prefusion state of respiratory syncytial virus (RSV) fusion (F) glycoprotein is the target of most RSV-neutralizing activity in human sera, but its metastability has hindered characterization. To overcome this obstacle, we identified prefusion-specific antibodies that were substantially more potent than the prophylactic antibody palivizumab. The cocrystal structure for one of these antibodies, D25, in complex with the F glycoprotein revealed D25 to lock F in its prefusion state by binding to a quaternary epitope at the trimer apex. Electron microscopy showed that two other antibodies, AM22 and 5C4, also bound to the newly identified site of vulnerability, which we named antigenic site O. These studies should enable design of improved vaccine antigens and define new targets for passive prevention of RSV-induced disease.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4459498/" 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/PMC4459498/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉McLellan, Jason S -- Chen, Man -- Leung, Sherman -- Graepel, Kevin W -- Du, Xiulian -- Yang, Yongping -- Zhou, Tongqing -- Baxa, Ulrich -- Yasuda, Etsuko -- Beaumont, Tim -- Kumar, Azad -- Modjarrad, Kayvon -- Zheng, Zizheng -- Zhao, Min -- Xia, Ningshao -- Kwong, Peter D -- Graham, Barney S -- ZIA AI005024-11/Intramural NIH HHS/ -- ZIA AI005061-10/Intramural NIH HHS/ -- New York, N.Y. -- Science. 2013 May 31;340(6136):1113-7. doi: 10.1126/science.1234914. Epub 2013 Apr 25.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. mclellanja@niaid.nih.gov〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23618766" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Amino Acid Sequence ; Animals ; Antibodies, Monoclonal, Humanized/immunology ; Antibodies, Neutralizing/chemistry/*immunology ; Crystallography, X-Ray ; Female ; Glycoproteins/chemistry/*immunology ; HEK293 Cells ; Humans ; Mice ; Mice, Inbred BALB C ; Molecular Sequence Data ; Neutralization Tests ; Palivizumab ; Protein Conformation ; Protein Multimerization ; Respiratory Syncytial Virus Vaccines/chemistry/*immunology ; Respiratory Syncytial Viruses/*immunology/physiology ; Viral Fusion Proteins/chemistry/*immunology ; Virus Internalization
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 185
    Publikationsdatum: 2013-09-14
    Beschreibung: The CCR5 chemokine receptor acts as a co-receptor for HIV-1 viral entry. Here we report the 2.7 angstrom-resolution crystal structure of human CCR5 bound to the marketed HIV drug maraviroc. The structure reveals a ligand-binding site that is distinct from the proposed major recognition sites for chemokines and the viral glycoprotein gp120, providing insights into the mechanism of allosteric inhibition of chemokine signaling and viral entry. A comparison between CCR5 and CXCR4 crystal structures, along with models of co-receptor-gp120-V3 complexes, suggests that different charge distributions and steric hindrances caused by residue substitutions may be major determinants of HIV-1 co-receptor selectivity. These high-resolution insights into CCR5 can enable structure-based drug discovery for the treatment of HIV-1 infection.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3819204/" 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/PMC3819204/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tan, Qiuxiang -- Zhu, Ya -- Li, Jian -- Chen, Zhuxi -- Han, Gye Won -- Kufareva, Irina -- Li, Tingting -- Ma, Limin -- Fenalti, Gustavo -- Li, Jing -- Zhang, Wenru -- Xie, Xin -- Yang, Huaiyu -- Jiang, Hualiang -- Cherezov, Vadim -- Liu, Hong -- Stevens, Raymond C -- Zhao, Qiang -- Wu, Beili -- R01 AI100604/AI/NIAID NIH HHS/ -- R01 GM071872/GM/NIGMS NIH HHS/ -- U01 GM094612/GM/NIGMS NIH HHS/ -- U54 GM094618/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2013 Sep 20;341(6152):1387-90. doi: 10.1126/science.1241475. Epub 2013 Sep 12.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Pudong, Shanghai, China 201203.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24030490" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Binding Sites ; Cyclohexanes/*chemistry/pharmacology ; HIV Envelope Protein gp120/metabolism ; HIV Fusion Inhibitors/*chemistry/pharmacology ; HIV-1/*drug effects/physiology ; Humans ; Ligands ; Protein Conformation ; Receptors, CCR5/*chemistry/metabolism ; Receptors, CXCR4/chemistry ; Triazoles/*chemistry/pharmacology ; Virus Internalization/*drug effects
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 186
    Publikationsdatum: 2012-12-01
    Beschreibung: The Trypanosoma brucei cysteine protease cathepsin B (TbCatB), which is involved in host protein degradation, is a promising target to develop new treatments against sleeping sickness, a fatal disease caused by this protozoan parasite. The structure of the mature, active form of TbCatB has so far not provided sufficient information for the design of a safe and specific drug against T. brucei. By combining two recent innovations, in vivo crystallization and serial femtosecond crystallography, we obtained the room-temperature 2.1 angstrom resolution structure of the fully glycosylated precursor complex of TbCatB. The structure reveals the mechanism of native TbCatB inhibition and demonstrates that new biomolecular information can be obtained by the "diffraction-before-destruction" approach of x-ray free-electron lasers from hundreds of thousands of individual microcrystals.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3786669/" 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/PMC3786669/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Redecke, Lars -- Nass, Karol -- DePonte, Daniel P -- White, Thomas A -- Rehders, Dirk -- Barty, Anton -- Stellato, Francesco -- Liang, Mengning -- Barends, Thomas R M -- Boutet, Sebastien -- Williams, Garth J -- Messerschmidt, Marc -- Seibert, M Marvin -- Aquila, Andrew -- Arnlund, David -- Bajt, Sasa -- Barth, Torsten -- Bogan, Michael J -- Caleman, Carl -- Chao, Tzu-Chiao -- Doak, R Bruce -- Fleckenstein, Holger -- Frank, Matthias -- Fromme, Raimund -- Galli, Lorenzo -- Grotjohann, Ingo -- Hunter, Mark S -- Johansson, Linda C -- Kassemeyer, Stephan -- Katona, Gergely -- Kirian, Richard A -- Koopmann, Rudolf -- Kupitz, Chris -- Lomb, Lukas -- Martin, Andrew V -- Mogk, Stefan -- Neutze, Richard -- Shoeman, Robert L -- Steinbrener, Jan -- Timneanu, Nicusor -- Wang, Dingjie -- Weierstall, Uwe -- Zatsepin, Nadia A -- Spence, John C H -- Fromme, Petra -- Schlichting, Ilme -- Duszenko, Michael -- Betzel, Christian -- Chapman, Henry N -- 1R01GM095583/GM/NIGMS NIH HHS/ -- R01 GM095583/GM/NIGMS NIH HHS/ -- U54 GM094599/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2013 Jan 11;339(6116):227-30. doi: 10.1126/science.1229663. Epub 2012 Nov 29.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Joint Laboratory for Structural Biology of Infection and Inflammation, Institute of Biochemistry and Molecular Biology, University of Hamburg, and Institute of Biochemistry, University of Lubeck, at Deutsches Elektronen-Synchrotron, Notkestrasse 85, 22607 Hamburg, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23196907" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Amino Acid Sequence ; Animals ; Catalytic Domain ; Cathepsin B/antagonists & inhibitors/*chemistry ; Crystallization ; Crystallography, X-Ray ; Enzyme Precursors/chemistry ; Glycosylation ; Models, Molecular ; Molecular Sequence Data ; Protein Conformation ; Protozoan Proteins/antagonists & inhibitors/*chemistry ; Sf9 Cells ; Spodoptera ; Trypanosoma brucei brucei/*enzymology ; X-Rays
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 187
    facet.materialart.
    Unbekannt
    American Association for the Advancement of Science (AAAS)
    Publikationsdatum: 2013-07-03
    Beschreibung: Protein synthesis by the ribosome requires the translocation of transfer RNAs and messenger RNA by one codon after each peptide bond is formed, a reaction that requires ribosomal subunit rotation and is catalyzed by the guanosine triphosphatase (GTPase) elongation factor G (EF-G). We determined 3 angstrom resolution x-ray crystal structures of EF-G complexed with a nonhydrolyzable guanosine 5'-triphosphate (GTP) analog and bound to the Escherichia coli ribosome in different states of ribosomal subunit rotation. The structures reveal that EF-G binding to the ribosome stabilizes switch regions in the GTPase active site, resulting in a compact EF-G conformation that favors an intermediate state of ribosomal subunit rotation. These structures suggest that EF-G controls the translocation reaction by cycles of conformational rigidity and relaxation before and after GTP hydrolysis.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4274944/" 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/PMC4274944/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pulk, Arto -- Cate, Jamie H D -- R01 GM065050/GM/NIGMS NIH HHS/ -- R01 GM105404/GM/NIGMS NIH HHS/ -- R01-GM65050/GM/NIGMS NIH HHS/ -- R01GM105404/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2013 Jun 28;340(6140):1235970. doi: 10.1126/science.1235970.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Cell Biology, California Institute for Quantitative Biosciences, University of California, Berkeley, CA 94720, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23812721" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Crystallography, X-Ray ; Escherichia coli/*enzymology ; Guanosine Triphosphate/*chemistry ; Hydrolysis ; Models, Biological ; Peptide Elongation Factor G/*chemistry ; *Protein Biosynthesis ; Protein Conformation ; Protein Structure, Tertiary ; RNA, Messenger/chemistry ; RNA, Transfer/chemistry ; Ribosome Subunits, Large, Bacterial/*chemistry ; Rotation
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 188
    facet.materialart.
    Unbekannt
    American Association for the Advancement of Science (AAAS)
    Publikationsdatum: 2013-01-26
    Beschreibung: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bowie, James U -- R01GM063919/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2013 Jan 25;339(6118):398-9. doi: 10.1126/science.1228655.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry and Biochemistry, UCLA-DOE Institute of Genomics and Proteomics, University of California, Los Angeles, Los Angeles, CA 90095, USA. bowie@mbi.ucla.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23349275" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Cell Membrane/*chemistry ; Hydrogen Bonding ; Lipid Bilayers/chemistry ; Membrane Proteins/*chemistry ; Models, Molecular ; Protein Conformation ; *Protein Folding ; Protein Structure, Secondary ; Protein Subunits/chemistry
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 189
    Publikationsdatum: 2013-05-11
    Beschreibung: 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〉
    Schlagwort(e): 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
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 190
    Publikationsdatum: 2013-05-04
    Beschreibung: 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〉
    Schlagwort(e): 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 ; Mutation ; Oligosaccharides/chemistry/metabolism ; Protein Binding ; Protein Conformation ; Protein Stability ; Receptors, Cell Surface/chemistry/*metabolism ; Receptors, Virus/chemistry/*metabolism ; Recombinant Proteins/chemistry/metabolism
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 191
    Publikationsdatum: 2013-08-31
    Beschreibung: Tissues can be soft like fat, which bears little stress, or stiff like bone, which sustains high stress, but whether there is a systematic relationship between tissue mechanics and differentiation is unknown. Here, proteomics analyses revealed that levels of the nucleoskeletal protein lamin-A scaled with tissue elasticity, E, as did levels of collagens in the extracellular matrix that determine E. Stem cell differentiation into fat on soft matrix was enhanced by low lamin-A levels, whereas differentiation into bone on stiff matrix was enhanced by high lamin-A levels. Matrix stiffness directly influenced lamin-A protein levels, and, although lamin-A transcription was regulated by the vitamin A/retinoic acid (RA) pathway with broad roles in development, nuclear entry of RA receptors was modulated by lamin-A protein. Tissue stiffness and stress thus increase lamin-A levels, which stabilize the nucleus while also contributing to lineage determination.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3976548/" 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/PMC3976548/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Swift, Joe -- Ivanovska, Irena L -- Buxboim, Amnon -- Harada, Takamasa -- Dingal, P C Dave P -- Pinter, Joel -- Pajerowski, J David -- Spinler, Kyle R -- Shin, Jae-Won -- Tewari, Manorama -- Rehfeldt, Florian -- Speicher, David W -- Discher, Dennis E -- 8UL1TR000003/TR/NCATS NIH HHS/ -- CA010815/CA/NCI NIH HHS/ -- HL038794/HL/NHLBI NIH HHS/ -- P01DK032094/DK/NIDDK NIH HHS/ -- P30-DK090969/DK/NIDDK NIH HHS/ -- R01 EB007049/EB/NIBIB NIH HHS/ -- R01 HL062352/HL/NHLBI NIH HHS/ -- R01EB007049/EB/NIBIB NIH HHS/ -- R01HL062352/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2013 Aug 30;341(6149):1240104. doi: 10.1126/science.1240104.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Molecular and Cell Biophysics Laboratory, University of Pennsylvania, Philadelphia, PA 19104, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23990565" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Adipogenesis ; Animals ; *Cell Differentiation ; Collagen/analysis/chemistry/metabolism ; *Elasticity ; Extracellular Matrix/chemistry/metabolism ; Gene Expression Regulation, Developmental ; Humans ; Lamin Type A/chemistry/genetics/*metabolism ; Mesenchymal Stromal Cells/*cytology ; Mice ; Models, Biological ; Nuclear Lamina/metabolism ; *Osteogenesis/genetics ; Protein Conformation ; Proteome ; *Stress, Mechanical ; Transcription, Genetic ; Tretinoin/metabolism ; Vitamin A/metabolism
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  • 192
    Publikationsdatum: 2013-07-03
    Beschreibung: Translocation of messenger and transfer RNA (mRNA and tRNA) through the ribosome is a crucial step in protein synthesis, whose mechanism is not yet understood. The crystal structures of three Thermus ribosome-tRNA-mRNA-EF-G complexes trapped with beta,gamma-imidoguanosine 5'-triphosphate (GDPNP) or fusidic acid reveal conformational changes occurring during intermediate states of translocation, including large-scale rotation of the 30S subunit head and body. In all complexes, the tRNA acceptor ends occupy the 50S subunit E site, while their anticodon stem loops move with the head of the 30S subunit to positions between the P and E sites, forming chimeric intermediate states. Two universally conserved bases of 16S ribosomal RNA that intercalate between bases of the mRNA may act as "pawls" of a translocational ratchet. These findings provide new insights into the molecular mechanism of ribosomal translocation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3979973/" 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/PMC3979973/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhou, Jie -- Lancaster, Laura -- Donohue, John Paul -- Noller, Harry F -- GM-105404/GM/NIGMS NIH HHS/ -- GM-17129/GM/NIGMS NIH HHS/ -- GM-59140/GM/NIGMS NIH HHS/ -- P41-GM-103393/GM/NIGMS NIH HHS/ -- R01 GM017129/GM/NIGMS NIH HHS/ -- R01 GM059140/GM/NIGMS NIH HHS/ -- R01 GM105404/GM/NIGMS NIH HHS/ -- Y1-CO-1020/CO/NCI NIH HHS/ -- Y1-GM-1104/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2013 Jun 28;340(6140):1236086. doi: 10.1126/science.1236086.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Molecular Biology of RNA and Department of Molecular, Cell and Developmental Biology, University of California, Santa Cruz, CA 95064, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23812722" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Crystallography, X-Ray ; Fusidic Acid/chemistry ; Guanosine Triphosphate/analogs & derivatives/chemistry ; Peptide Elongation Factor G/*chemistry ; *Protein Biosynthesis ; Protein Conformation ; RNA, Messenger/chemistry ; RNA, Transfer/chemistry ; Ribosome Subunits, Large, Bacterial/*chemistry ; Thermus thermophilus/*enzymology
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  • 193
    Publikationsdatum: 2014-04-05
    Beschreibung: 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〉
    Schlagwort(e): 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
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  • 194
    Publikationsdatum: 2014-10-18
    Beschreibung: Potassium channels selectively conduct K(+) ions across cellular membranes with extraordinary efficiency. Their selectivity filter exhibits four binding sites with approximately equal electron density in crystal structures with high K(+) concentrations, previously thought to reflect a superposition of alternating ion- and water-occupied states. Consequently, cotranslocation of ions with water has become a widely accepted ion conduction mechanism for potassium channels. By analyzing more than 1300 permeation events from molecular dynamics simulations at physiological voltages, we observed instead that permeation occurs via ion-ion contacts between neighboring K(+) ions. Coulomb repulsion between adjacent ions is found to be the key to high-efficiency K(+) conduction. Crystallographic data are consistent with directly neighboring K(+) ions in the selectivity filter, and our model offers an intuitive explanation for the high throughput rates of K(+) channels.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kopfer, David A -- Song, Chen -- Gruene, Tim -- Sheldrick, George M -- Zachariae, Ulrich -- de Groot, Bert L -- New York, N.Y. -- Science. 2014 Oct 17;346(6207):352-5. doi: 10.1126/science.1254840.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Biomolecular Dynamics Group, Max Planck Institute for Biophysical Chemistry, 37077 Gottingen, Germany. ; Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UK. sc3210@gmail.com u.zachariae@dundee.ac.uk bgroot@gwdg.de. ; Department of Structural Chemistry, University of Gottingen, 37077 Gottingen, Germany. ; School of Engineering, Physics and Mathematics, University of Dundee, Dundee DD1 4HN, UK. College of Life Sciences, University of Dundee, Dundee DD1 5EH, UK. sc3210@gmail.com u.zachariae@dundee.ac.uk bgroot@gwdg.de. ; Biomolecular Dynamics Group, Max Planck Institute for Biophysical Chemistry, 37077 Gottingen, Germany. sc3210@gmail.com u.zachariae@dundee.ac.uk bgroot@gwdg.de.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25324389" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Bacterial Proteins/*chemistry/metabolism ; Binding Sites ; Crystallography, X-Ray ; Molecular Dynamics Simulation ; Potassium/*metabolism ; Potassium Channels/*chemistry/metabolism ; Protein Conformation ; *Static Electricity ; Water
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  • 195
    Publikationsdatum: 2014-12-20
    Beschreibung: Evolution and design of protein complexes are almost always viewed through the lens of amino acid mutations at protein interfaces. We showed previously that residues not involved in the physical interaction between proteins make important contributions to oligomerization by acting indirectly or allosterically. In this work, we sought to investigate the mechanism by which allosteric mutations act, using the example of the PyrR family of pyrimidine operon attenuators. In this family, a perfectly sequence-conserved helix that forms a tetrameric interface is exposed as solvent-accessible surface in dimeric orthologs. This means that mutations must be acting from a distance to destabilize the interface. We identified 11 key mutations controlling oligomeric state, all distant from the interfaces and outside ligand-binding pockets. Finally, we show that the key mutations introduce conformational changes equivalent to the conformational shift between the free versus nucleotide-bound conformations of the proteins.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4337988/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4337988/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Perica, Tina -- Kondo, Yasushi -- Tiwari, Sandhya P -- McLaughlin, Stephen H -- Kemplen, Katherine R -- Zhang, Xiuwei -- Steward, Annette -- Reuter, Nathalie -- Clarke, Jane -- Teichmann, Sarah A -- 095195/Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2014 Dec 19;346(6216):1254346. doi: 10.1126/science.1254346.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK. Medical Research Council (MRC) Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge CB2 0QH, UK. ; Medical Research Council (MRC) Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge CB2 0QH, UK. ; Department of Molecular Biology, University of Bergen University of Bergen, P.O. Box 7803, N-5020 Bergen, Norway. Computational Biology Unit, Department of Informatics, University of Bergen, P.O. Box 7803, N-5020 Bergen, Norway. ; Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK. ; European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK. ; European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK. saraht@ebi.ac.uk.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25525255" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Allosteric Regulation/*genetics ; Amino Acid Sequence ; Bacillus subtilis/metabolism ; Bacterial Proteins/*chemistry/genetics ; Conserved Sequence ; *Evolution, Molecular ; Ligands ; Mutation ; Pentosyltransferases/*chemistry/genetics ; Protein Binding/genetics ; Protein Conformation ; *Protein Engineering ; Protein Multimerization/*genetics ; Repressor Proteins/*chemistry/genetics
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  • 196
    Publikationsdatum: 2014-09-06
    Beschreibung: Coupled translocation of messenger RNA and transfer RNA (tRNA) through the ribosome, a process catalyzed by elongation factor EF-G, is a crucial step in protein synthesis. The crystal structure of a bacterial translocation complex describes the binding states of two tRNAs trapped in mid-translocation. The deacylated P-site tRNA has moved into a partly translocated pe/E chimeric hybrid state. The anticodon stem-loop of the A-site tRNA is captured in transition toward the 30S P site, while its 3' acceptor end contacts both the A and P loops of the 50S subunit, forming an ap/ap chimeric hybrid state. The structure shows how features of ribosomal RNA rearrange to hand off the A-site tRNA to the P site, revealing an active role for ribosomal RNA in the translocation process.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4242719/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4242719/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhou, Jie -- Lancaster, Laura -- Donohue, John Paul -- Noller, Harry F -- GM-17129/GM/NIGMS NIH HHS/ -- GM59140/GM/NIGMS NIH HHS/ -- R01 GM017129/GM/NIGMS NIH HHS/ -- R01 GM059140/GM/NIGMS NIH HHS/ -- R01 GM105404/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2014 Sep 5;345(6201):1188-91. doi: 10.1126/science.1255030.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Molecular Biology of RNA and Department of Molecular, Cell and Developmental Biology, University of California at Santa Cruz, Santa Cruz, CA 95064, USA. ; Center for Molecular Biology of RNA and Department of Molecular, Cell and Developmental Biology, University of California at Santa Cruz, Santa Cruz, CA 95064, USA. harry@nuvolari.ucsc.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25190797" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Anticodon/chemistry/metabolism ; Binding Sites ; Catalysis ; Crystallography, X-Ray ; Nucleic Acid Conformation ; Peptide Elongation Factor G/*chemistry/metabolism ; Protein Biosynthesis ; Protein Conformation ; RNA, Messenger/*chemistry/metabolism ; RNA, Transfer/*chemistry/metabolism ; Ribosome Subunits, Large, Bacterial/*chemistry/metabolism ; Thermus thermophilus
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  • 197
    Publikationsdatum: 2014-04-20
    Beschreibung: 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〉
    Schlagwort(e): 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
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  • 198
    Publikationsdatum: 2014-10-18
    Beschreibung: Human bestrophin-1 (hBest1) is a calcium-activated chloride channel from the retinal pigment epithelium, where mutations are associated with vitelliform macular degeneration, or Best disease. We describe the structure of a bacterial homolog (KpBest) of hBest1 and functional characterizations of both channels. KpBest is a pentamer that forms a five-helix transmembrane pore, closed by three rings of conserved hydrophobic residues, and has a cytoplasmic cavern with a restricted exit. From electrophysiological analysis of structure-inspired mutations in KpBest and hBest1, we find a sensitive control of ion selectivity in the bestrophins, including reversal of anion/cation selectivity, and dramatic activation by mutations at the cytoplasmic exit. A homology model of hBest1 shows the locations of disease-causing mutations and suggests possible roles in regulation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4341822/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4341822/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yang, Tingting -- Liu, Qun -- Kloss, Brian -- Bruni, Renato -- Kalathur, Ravi C -- Guo, Youzhong -- Kloppmann, Edda -- Rost, Burkhard -- Colecraft, Henry M -- Hendrickson, Wayne A -- GM095315/GM/NIGMS NIH HHS/ -- GM107462/GM/NIGMS NIH HHS/ -- R01 GM107462/GM/NIGMS NIH HHS/ -- U54 GM075026/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2014 Oct 17;346(6207):355-9. doi: 10.1126/science.1259723. Epub 2014 Sep 25.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA. ; New York Structural Biology Center, Synchrotron Beamlines, Brookhaven National Laboratory, Upton, NY 11973, USA. ; New York Consortium on Membrane Protein Structure, New York Structural Biology Center, 89 Convent Avenue, New York, NY 10027, USA. ; New York Consortium on Membrane Protein Structure, New York Structural Biology Center, 89 Convent Avenue, New York, NY 10027, USA. Department of Informatics, Bioinformatics and Computational Biology, TUM (Technische Universitat Munchen), Garching 85748, Germany. ; Department of Physiology and Cellular Biophysics, Columbia University, New York, NY 10032, USA. ; Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA. New York Structural Biology Center, Synchrotron Beamlines, Brookhaven National Laboratory, Upton, NY 11973, USA. New York Consortium on Membrane Protein Structure, New York Structural Biology Center, 89 Convent Avenue, New York, NY 10027, USA. Department of Physiology and Cellular Biophysics, Columbia University, New York, NY 10032, USA. wayne@xtl.cumc.columbia.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25324390" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Bacterial Proteins/*chemistry ; Chloride Channels/*chemistry ; Crystallography, X-Ray ; Electric Conductivity ; Eye Proteins/*chemistry ; Humans ; *Klebsiella pneumoniae ; Protein Conformation ; Static Electricity
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  • 199
    Publikationsdatum: 2014-03-08
    Beschreibung: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Coontz, Robert -- Fahrenkamp-Uppenbrink, Julia -- Lavine, Marc -- Vinson, Valda -- New York, N.Y. -- Science. 2014 Mar 7;343(6175):1091. doi: 10.1126/science.343.6175.1091.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24604190" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Crystallography, X-Ray/*history/trends ; Databases, Protein ; History, 20th Century ; History, 21st Century ; Protein Conformation
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 200
    Publikationsdatum: 2014-12-06
    Beschreibung: Serial femtosecond crystallography using ultrashort pulses from x-ray free electron lasers (XFELs) enables studies of the light-triggered dynamics of biomolecules. We used microcrystals of photoactive yellow protein (a bacterial blue light photoreceptor) as a model system and obtained high-resolution, time-resolved difference electron density maps of excellent quality with strong features; these allowed the determination of structures of reaction intermediates to a resolution of 1.6 angstroms. Our results open the way to the study of reversible and nonreversible biological reactions on time scales as short as femtoseconds under conditions that maximize the extent of reaction initiation throughout the crystal.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4361027/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4361027/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tenboer, Jason -- Basu, Shibom -- Zatsepin, Nadia -- Pande, Kanupriya -- Milathianaki, Despina -- Frank, Matthias -- Hunter, Mark -- Boutet, Sebastien -- Williams, Garth J -- Koglin, Jason E -- Oberthuer, Dominik -- Heymann, Michael -- Kupitz, Christopher -- Conrad, Chelsie -- Coe, Jesse -- Roy-Chowdhury, Shatabdi -- Weierstall, Uwe -- James, Daniel -- Wang, Dingjie -- Grant, Thomas -- Barty, Anton -- Yefanov, Oleksandr -- Scales, Jennifer -- Gati, Cornelius -- Seuring, Carolin -- Srajer, Vukica -- Henning, Robert -- Schwander, Peter -- Fromme, Raimund -- Ourmazd, Abbas -- Moffat, Keith -- Van Thor, Jasper J -- Spence, John C H -- Fromme, Petra -- Chapman, Henry N -- Schmidt, Marius -- P41 GM103543/GM/NIGMS NIH HHS/ -- R01GM095583/GM/NIGMS NIH HHS/ -- R24 GM111072/GM/NIGMS NIH HHS/ -- R24GM111072/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2014 Dec 5;346(6214):1242-6. doi: 10.1126/science.1259357.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Physics Department, University of Wisconsin, Milwaukee, WI 53211, USA. ; Department of Chemistry and Biochemistry, Arizona State University, Tempe, AZ 85287, USA. ; Department of Physics, Arizona State University, Tempe, AZ 85287, USA. ; Linac Coherent Light Source, SLAC National Accelerator Laboratory, Sand Hill Road, Menlo Park, CA 94025, USA. ; Lawrence Livermore National Laboratory, Livermore, CA 94550, USA. ; Centre for Ultrafast Imaging, University of Hamburg, 22761 Hamburg, Germany. ; Center for Free Electron Laser Science, Deutsches Elektronen Synchrotron DESY, Notkestrasse 85, 22607 Hamburg, Germany. ; Hauptman-Woodward Institute, State University of New York at Buffalo, 700 Ellicott Street, Buffalo, NY 14203, USA. ; Centre for Ultrafast Imaging, University of Hamburg, 22761 Hamburg, Germany. Center for Free Electron Laser Science, Deutsches Elektronen Synchrotron DESY, Notkestrasse 85, 22607 Hamburg, Germany. ; Center for Advanced Radiation Sources, University of Chicago, Chicago, IL 60637, USA. ; Center for Advanced Radiation Sources, University of Chicago, Chicago, IL 60637, USA. Department of Biochemistry and Molecular Biology and Institute for Biophysical Dynamics, University of Chicago, Chicago, IL 60637, USA. ; Department of Biochemistry and Molecular Biology and Institute for Biophysical Dynamics, University of Chicago, Chicago, IL 60637, USA. ; Physics Department, University of Wisconsin, Milwaukee, WI 53211, USA. m-schmidt@uwm.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25477465" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Bacterial Proteins/chemistry/*ultrastructure ; Crystallography, X-Ray/*methods ; Photoreceptors, Microbial/chemistry/*ultrastructure ; Protein Conformation ; Time Factors
    Print ISSN: 0036-8075
    Digitale ISSN: 1095-9203
    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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