biomolecules-12-00600-v2.pdf (5.63 MB)
Advances towards understanding the mechanism of action of the Hsp90 Complex
journal contribution
posted on 2023-06-10, 03:32 authored by Chrisostomos ProdromouChrisostomos Prodromou, Dennis BjorklundHsp90 (Heat Shock Protein 90) is an ATP (Adenosine triphosphate) molecular chaperone responsible for the activation and maturation of client proteins. The mechanism by which Hsp90 achieves such activation, involving structurally diverse client proteins, has remained enigmatic. However, recent advances using structural techniques, together with advances in biochemical studies, have not only defined the chaperone cycle but have shed light on its mechanism of action. Hsp90 hydrolysis of ATP by each protomer may not be simultaneous and may be dependent on the specific client protein and co-chaperone complex involved. Surprisingly, Hsp90 appears to remodel client proteins, acting as a means by which the structure of the client protein is modified to allow its subsequent refolding to an active state, in the case of kinases, or by making the client protein competent for hormone binding, as in the case of the GR (glucocorticoid receptor). This review looks at selected examples of client proteins, such as CDK4 (cyclin-dependent kinase 4) and GR, which are activated according to the so-called ‘remodelling hypothesis’ for their activation. A detailed description of these activation mechanisms is paramount to understanding how Hsp90-associated diseases develop.
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- Published
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- Published version
Journal
BiomoleculesISSN
2218-273XPublisher
MDPIExternal DOI
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5Volume
12Page range
1-23Article number
a600Department affiliated with
- Biochemistry Publications
Full text available
- Yes
Peer reviewed?
- Yes
Legacy Posted Date
2022-05-16First Open Access (FOA) Date
2022-05-16First Compliant Deposit (FCD) Date
2022-05-13Usage metrics
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