Advances towards understanding the mechanism of action of the Hsp90 Complex

Prodromou, Chrisostomos and Bjorklund, Dennis M (2022) Advances towards understanding the mechanism of action of the Hsp90 Complex. Biomolecules, 12 (5). a600 1-23. ISSN 2218-273X

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Hsp90 (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.

Item Type: Article
Keywords: chaperone, co-chaperone, heat shock proteins, Hsp90; Aha1, immunophilins, p23, Cdc37, kinase, steroid hormone receptor, structure, mechanism, ATPase
Schools and Departments: School of Life Sciences > Biochemistry
Subjects: Q Science > QD Chemistry > QD0901 Crystallography > QD0921 Crystal structure and growth
Q Science > QH Natural history > QH0301 Biology
Depositing User: Chrisostomos Prodromou
Date Deposited: 16 May 2022 08:05
Last Modified: 16 May 2022 08:15

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