| An interdomain energetic tug-of-war creates the allosterically active state in Hsp70 molecular chaperones. | |
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MedLine Citation:
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PMID: 23217711 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The allosteric mechanism of Hsp70 molecular chaperones enables ATP binding to the N-terminal nucleotide-binding domain (NBD) to alter substrate affinity to the C-terminal substrate-binding domain (SBD) and substrate binding to enhance ATP hydrolysis. Cycling between ATP-bound and ADP/substrate-bound states requires Hsp70s to visit a state with high ATPase activity and fast on/off kinetics of substrate binding. We have trapped this "allosterically active" state for the E. coli Hsp70, DnaK, and identified how interactions among the NBD, the β subdomain of the SBD, the SBD α-helical lid, and the conserved hydrophobic interdomain linker enable allosteric signal transmission between ligand-binding sites. Allostery in Hsp70s results from an energetic tug-of-war between domain conformations and formation of two orthogonal interfaces: between the NBD and SBD, and between the helical lid and the β subdomain of the SBD. The resulting energetic tension underlies Hsp70 functional properties and enables them to be modulated by ligands and cochaperones and "tuned" through evolution. |
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Authors:
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Anastasia Zhuravleva; Eugenia M Clerico; Lila M Gierasch |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural |
Journal Detail:
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Title: Cell Volume: 151 ISSN: 1097-4172 ISO Abbreviation: Cell Publication Date: 2012 Dec |
Date Detail:
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Created Date: 2012-12-10 Completed Date: 2013-02-06 Revised Date: 2013-04-16 |
Medline Journal Info:
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Nlm Unique ID: 0413066 Medline TA: Cell Country: United States |
Other Details:
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Languages: eng Pagination: 1296-307 Citation Subset: IM |
Copyright Information:
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Copyright © 2012 Elsevier Inc. All rights reserved. |
Affiliation:
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Department of Biochemistry and Molecular Biology, University of Massachusetts, Amherst, MA 01003, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adenosine Diphosphate
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metabolism Adenosine Triphosphate / metabolism Allosteric Regulation Amino Acid Sequence Catalytic Domain Escherichia coli / metabolism* Escherichia coli Proteins / chemistry*, genetics, metabolism* HSP70 Heat-Shock Proteins / chemistry*, genetics, metabolism* Models, Molecular Molecular Sequence Data Mutation Nuclear Magnetic Resonance, Biomolecular Protein Conformation Protein Structure, Tertiary Sequence Alignment |
| Grant Support | |
ID/Acronym/Agency:
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GM027616/GM/NIGMS NIH HHS; R01 GM027616/GM/NIGMS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Escherichia coli Proteins; 0/HSP70 Heat-Shock Proteins; 56-65-5/Adenosine Triphosphate; 58-64-0/Adenosine Diphosphate; EC 3.6.1.-/dnaK protein, E coli |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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