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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.

Original publication




Journal article


J Mol Biol

Publication Date





891 - 907


Absorption, Adenosine Triphosphatases, Adenosine Triphosphate, Calibration, Cell Cycle Proteins, Chaperonins, Chromatography, Gel, Dimerization, Drosophila Proteins, Electrophoresis, Polyacrylamide Gel, Escherichia coli, Genetic Variation, HSP90 Heat-Shock Proteins, Humans, Least-Squares Analysis, Models, Biological, Molecular Chaperones, Peptides, Protein Binding, Protein Structure, Tertiary, Recombinant Fusion Proteins, Solutions, Spectrometry, Fluorescence, Subtilisin, Ultracentrifugation, X-Ray Diffraction