Document Type
Article
Publication Date
4-21-2016
Digital Object Identifier (DOI)
https://doi.org/10.1016/j.molcel.2016.04.005
Abstract
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-to-nonclient 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.
Rights Information
Was this content written or created while at USF?
Yes
Citation / Publisher Attribution
Molecular Cell, v. 62, issue 2, p. 260-271
This article is the post-print author version. Under a Creative Commons license.
Scholar Commons Citation
Keramisanou, Dimitra; Aboalroub, Adam; Zhang, Ziming; Liu, Wenjun; Marshall, Devon; Diviney, Andrea; Larsen, Randy W.; Landgraf, Ralf; and Gelis, Ioannis, "Molecular Mechanism of Protein Kinase Recognition and Sorting by the Hsp90 Kinome-Specific Cochaperone Cdc37" (2016). Chemistry Faculty Publications. 24.
https://digitalcommons.usf.edu/chm_facpub/24
Supplemental material
Graphical Abstract.PNG (497 kB)
Graphical abstract
