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Structure of an Hsp90-Cdc37-Cdk4 complex
journal contribution
posted on 2023-06-08, 14:44 authored by Cara K Vaughan, Ulrich Gohlke, Frank Sobott, Valerie M Good, Maruf M U Ali, Chrisostomos ProdromouChrisostomos Prodromou, Carol V Robinson, Helen R Saibil, Laurence PearlLaurence PearlActivation of many protein kinases depends on their interaction with the Hsp90 molecular chaperone system. Recruitment of protein kinase clients to the Hsp90 chaperone system is mediated by the cochaperone adaptor protein Cdc37, which acts as a scaffold, simultaneously binding protein kinases and Hsp90. We have now expressed and purified an Hsp90-Cdc37-Cdk4 complex, defined its stoichiometry, and determined its 3D structure by single-particle electron microscopy. Comparison with the crystal structure of Hsp90 allows us to identify the locations of Cdc37 and Cdk4 in the complex and suggests a mechanism by which conformational changes in the kinase are coupled to the Hsp90 ATPase cycle.
History
Publication status
- Published
File Version
- Published version
Journal
Molecular CellISSN
1097-2765Publisher
ElsevierExternal DOI
Issue
5Volume
23Page range
697-707Department affiliated with
- Biochemistry Publications
Full text available
- Yes
Peer reviewed?
- Yes
Legacy Posted Date
2015-02-24First Open Access (FOA) Date
2015-02-24First Compliant Deposit (FCD) Date
2015-02-24Usage metrics
Categories
No categories selectedKeywords
Cell Cycle Proteins/*chemistry/isolation & purification/*ultrastructureChaperonins/*chemistry/isolation & purification/*ultrastructureCyclin-Dependent Kinase 4/*chemistry/isolation & purification/*ultrastructureHSP90 Heat-Shock Proteins/*chemistry/isolation & purification/*ultrastructureHumansMicroscopyElectronModelsMolecularMultiprotein Complexes/chemistry/isolation & purification/ultrastructureProtein Binding