Structure of an Hsp90-Cdc37-Cdk4 complex.
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.
Vaughan
Cara K
CK
Section of Structural Biology, The Institute of Cancer Research, Chester Beatty Laboratories, London SW3 6JB, UK.
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
D018797:Cell Cycle Proteins / Q000737:chemistry* / Q000302:isolation & purification / Q000648:ultrastructure*; D018833:Chaperonins / Q000737:chemistry* / Q000302:isolation & purification / Q000648:ultrastructure*; D051358:Cyclin-Dependent Kinase 4 / Q000737:chemistry* / Q000302:isolation & purification / Q000648:ultrastructure*; D018841:HSP90 Heat-Shock Proteins / Q000737:chemistry* / Q000302:isolation & purification / Q000648:ultrastructure*; D006801:Humans; D008854:Microscopy, Electron; D008958:Models, Molecular; D046912:Multiprotein Complexes / Q000737:chemistry / Q000302:isolation & purification / Q000648:ultrastructure; D011485:Protein Binding
C498362:CDC37 protein, human; D018797:Cell Cycle Proteins; D018841:HSP90 Heat-Shock Proteins; D046912:Multiprotein Complexes; C495900:CDK4 protein, human; D051358:Cyclin-Dependent Kinase 4; D018833:Chaperonins