Molecular Cell
Molecular Cell
5 years ago

The Plasticity of the Hsp90 Co-chaperone System

The Plasticity of the Hsp90 Co-chaperone System
The Hsp90 system in the eukaryotic cytosol is characterized by a cohort of co-chaperones that bind to Hsp90 and affect its function. Although progress has been made regarding the underlying biochemical mechanisms, how co-chaperones influence Hsp90 client proteins in vivo has remained elusive. By investigating the effect of 12 Hsp90 co-chaperones on the activity of different client proteins in yeast, we find that deletion of co-chaperones can have a neutral or negative effect on client activity but can also lead to more active clients. Only a few co-chaperones are active on all clients studied. Closely related clients and even point mutants can depend on different co-chaperones. These effects are direct because differences in client-co-chaperone interactions can be reconstituted in vitro. Interestingly, some co-chaperones affect client conformation in vivo. Thus, co-chaperones adapt the Hsp90 cycle to the requirements of the client proteins, ensuring optimal activation.

Graphical abstract

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Teaser

A large cohort of co-chaperones enables Hsp90 to chaperone structurally and functionally diverse client proteins. Sahasrabudhe et al. show that the nature of the client protein dictates the contribution of a co-chaperone to its maturation. Analysis in yeast suggests that only a few co-chaperones are of general importance.

Publisher URL: www.sciencedirect.com/science

DOI: S1097276517305786

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