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Structural and functional analysis of the middle segment of hsp90: implications for ATP hydrolysis and client protein and cochaperone interactions
journal contribution
posted on 2023-06-08, 14:42 authored by Philipe Meyer, Chrisostomos ProdromouChrisostomos Prodromou, Bin Hu, Cara Vaughan, S Mark Roe, Barry Panaretou, Peter W Piper, Laurence PearlLaurence PearlActivation of client proteins by the Hsp90 molecular chaperone is dependent on binding and hydrolysis of ATP, which drives a molecular clamp via transient dimerization of the N-terminal domains. The crystal structure of the middle segment of yeast Hsp90 reveals considerable evolutionary divergence from the equivalent regions of other GHKL protein family members such as MutL and GyrB, including an additional domain of new fold. Using the known structure of the N-terminal nucleotide binding domain, a model for the Hsp90 dimer has been constructed. From this structure, residues implicated in the ATPase-coupled conformational cycle and in interactions with client proteins and the activating cochaperone Aha1 have been identified, and their roles functionally characterized in vitro and in vivo.
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Publication status
- Published
File Version
- Published version
Journal
Molecular CellISSN
1097-2765Publisher
ElsevierExternal DOI
Issue
3Volume
11Page range
647-658Department affiliated with
- Biochemistry Publications
Full text available
- Yes
Peer reviewed?
- Yes
Legacy Posted Date
2015-02-25First Open Access (FOA) Date
2015-02-25First Compliant Deposit (FCD) Date
2015-02-25Usage metrics
Categories
Keywords
Adenosine Triphosphatases/metabolismAdenosine Triphosphate/metabolismAmino Acid SequenceBinding SitesCell DivisionX-RayDNA Gyrase/metabolismDimerizationDose-Response RelationshipDrugEscherichia coli Proteins/metabolismFungal Proteins/chemistryHSP90 Heat-Shock Proteins/*chemistry/*metabolismHydrolysisModelsMolecularMolecular Sequence DataMutationOncogene Protein pp60(v-src)/metabolismPhenotypeProtein BindingProtein ConformationProtein StructureTertiaryStructure-Activity RelationshipTemperature
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