Document Detail


Biochemical and structural studies of the interaction of Cdc37 with Hsp90.
MedLine Citation:
PMID:  15223329     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The heat shock protein Hsp90 plays a key, but poorly understood role in the folding, assembly and activation of a large number of signal transduction molecules, in particular kinases and steroid hormone receptors. In carrying out these functions Hsp90 hydrolyses ATP as it cycles between ADP- and ATP-bound forms, and this ATPase activity is regulated by the transient association with a variety of co-chaperones. Cdc37 is one such co-chaperone protein that also has a role in client protein recognition, in that it is required for Hsp90-dependent folding and activation of a particular group of protein kinases. These include the cyclin-dependent kinases (Cdk) 4/6 and Cdk9, Raf-1, Akt and many others. Here, the biochemical details of the interaction of human Hsp90 beta and Cdc37 have been characterised. Small angle X-ray scattering (SAXS) was then used to study the solution structure of Hsp90 and its complexes with Cdc37. The results suggest a model for the interaction of Cdc37 with Hsp90, whereby a Cdc37 dimer binds the two N-terminal domain/linker regions in an Hsp90 dimer, fixing them in a single conformation that is presumably suitable for client protein recognition.
Authors:
Wei Zhang; Miriam Hirshberg; Stephen H McLaughlin; Greg A Lazar; J Günter Grossmann; Peter R Nielsen; Frank Sobott; Carol V Robinson; Sophie E Jackson; Ernest D Laue
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of molecular biology     Volume:  340     ISSN:  0022-2836     ISO Abbreviation:  J. Mol. Biol.     Publication Date:  2004 Jul 
Date Detail:
Created Date:  2004-06-29     Completed Date:  2004-08-03     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  2985088R     Medline TA:  J Mol Biol     Country:  England    
Other Details:
Languages:  eng     Pagination:  891-907     Citation Subset:  IM    
Affiliation:
Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1GA, UK.
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MeSH Terms
Descriptor/Qualifier:
Absorption
Adenosine Triphosphatases / metabolism
Adenosine Triphosphate / metabolism
Calibration
Cell Cycle Proteins / chemistry,  drug effects,  isolation & purification,  metabolism*
Chaperonins
Chromatography, Gel
Dimerization
Drosophila Proteins / chemistry,  drug effects,  isolation & purification,  metabolism*
Electrophoresis, Polyacrylamide Gel
Escherichia coli / genetics
Genetic Variation
HSP90 Heat-Shock Proteins / chemistry*,  drug effects,  isolation & purification,  metabolism*
Humans
Least-Squares Analysis
Models, Biological
Molecular Chaperones / chemistry*,  drug effects,  isolation & purification,  metabolism*
Peptides / drug effects,  genetics,  metabolism
Protein Binding
Protein Structure, Tertiary
Recombinant Fusion Proteins / isolation & purification,  metabolism
Solutions / chemistry
Spectrometry, Fluorescence
Subtilisin / pharmacology
Ultracentrifugation
X-Ray Diffraction
Chemical
Reg. No./Substance:
0/CDC37 protein, human; 0/Cell Cycle Proteins; 0/Drosophila Proteins; 0/HSP90 Heat-Shock Proteins; 0/Molecular Chaperones; 0/Peptides; 0/Recombinant Fusion Proteins; 0/Solutions; 56-65-5/Adenosine Triphosphate; EC 3.4.21.62/Subtilisin; EC 3.6.1.-/Adenosine Triphosphatases; EC 3.6.1.-/Chaperonins

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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