Title
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Biochemical and structural studies of the interaction of Cdc37 with Hsp90
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Author
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Abstract
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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 Hsp90β 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. |
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Language
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English
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Source (journal)
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Journal of molecular biology. - London
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Publication
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London
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2004
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ISSN
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0022-2836
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DOI
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10.1016/J.JMB.2004.05.007
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Volume/pages
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340
:4
(2004)
, p. 891-907
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ISI
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000222734300020
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Full text (Publisher's DOI)
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