Journal
MOLECULAR CELL
Volume 62, Issue 2, Pages 260-271Publisher
CELL PRESS
DOI: 10.1016/j.molcel.2016.04.005
Keywords
-
Categories
Funding
- American Cancer Society [IRG93-032-16]
- NIH [GM115854]
Ask authors/readers for more resources
Despite the essential functions of Hsp90, little is known about the mechanism that controls substrate entry into its chaperone cycle. We show that the role of Cdc37 cochaperone reaches beyond that of an adaptor protein and find that it participates in the selective recruitment of only client kinases. Cdc37 recognizes kinase specificity determinants in both clients and nonclients and acts as a general kinase scanning factor. Kinase sorting within the client-tononclient continuum relies on the ability of Cdc37 to challenge the conformational stability of clients by locally unfolding them. This metastable conformational state has high affinity for Cdc37 and forms stable complexes through a multidomain cochaperone interface. The interaction with nonclients is not accompanied by conformational changes of the substrate and results in substrate dissociation. Collectively, Cdc37 performs a quality control of protein kinases, where induced conformational instability acts as a flag for Hsp90 dependence and stable cochaperone association.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available