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The mechanism of Hsp90 regulation by the protein kinase-specific cochaperone p50(cdc37)
journal contribution
posted on 2023-06-08, 14:43 authored by S Mark Roe, Maruf M U Ali, Philippe Meyer, Cara K Vaughan, Barry Panaretou, Peter W Piper, Chrisostomos ProdromouChrisostomos Prodromou, Laurence PearlLaurence PearlRecruitment of protein kinase clients to the Hsp90 chaperone involves the cochaperone p50(cdc37) acting as a scaffold, binding protein kinases via its N-terminal domain and Hsp90 via its C-terminal region. p50(cdc37) also has a regulatory activity, arresting Hsp90's ATPase cycle during client-protein loading. We have localized the binding site for p50(cdc37) to the N-terminal nucleotide binding domain of Hsp90 and determined the crystal structure of the Hsp90-p50(cdc37) core complex. Dimeric p50(cdc37) binds to surfaces of the Hsp90 N-domain implicated in ATP-dependent N-terminal dimerization and association with the middle segment of the chaperone. This interaction fixes the lid segment in an open conformation, inserts an arginine side chain into the ATP binding pocket to disable catalysis, and prevents trans-activating interaction of the N domains.
History
Publication status
- Published
Journal
CellISSN
0092-8674Publisher
ElsevierExternal DOI
Issue
1Volume
116Page range
87-98Department affiliated with
- Biochemistry Publications
Full text available
- No
Peer reviewed?
- Yes
Legacy Posted Date
2015-02-25Usage metrics
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No categories selectedKeywords
Adenosine Triphosphate/metabolismArginine/metabolismBinding Sites/physiologyCell Cycle Proteins/*metabolismDimerization*Drosophila ProteinsHSP90 Heat-Shock Proteins/*metabolismModelsMolecularMolecular Chaperones/*metabolismMolecular Sequence DataMolecular StructureProtein Binding/physiologyProtein ConformationProtein Kinases/*metabolismProtein StructureTertiary/physiologySequence HomologyAmino Acid
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