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Structure of an Hsp90-Cdc37-Cdk4 complex.

ABSTRACT: Activation 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.

SUBMITTER: Vaughan CK

PROVIDER: S-EPMC5704897 | biostudies-literature | 2006 Sep

REPOSITORIES: biostudies-literature

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Structure of an Hsp90-Cdc37-Cdk4 complex.

Vaughan Cara K CK Gohlke Ulrich U Sobott Frank F Good Valerie M VM Ali Maruf M U MM Prodromou Chrisostomos C Robinson Carol V CV Saibil Helen R HR Pearl Laurence H LH

Molecular cell 20060901 5

Activation 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 stru ...[more]

PMID: 16949366

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Atomic structure of Hsp90-Cdc37-Cdk4 reveals that Hsp90 traps and stabilizes an unfolded kinase.

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