NudC guides client transfer between the Hsp40/70 and Hsp90 chaperone systems.

Authors :: Biebl MM
Delhommel F
Faust O
Zak KM
Agam G
Guo X
Mühlhofer M
Dahiya V
Hillebrand D
Popowicz GM
Kampmann M
Lamb DC
Rosenzweig R
Sattler M
Buchner J
Source :: Molecular cell [Mol Cell] 2022 Feb 03; Vol. 82 (3), pp. 555-569.e7. Date of Electronic Publication: 2022 Jan 20.
Publication Year :: 2022
Abstract: In the eukaryotic cytosol, the Hsp70 and the Hsp90 chaperone machines work in tandem with the maturation of a diverse array of client proteins. The transfer of nonnative clients between these systems is essential to the chaperoning process, but how it is regulated is still not clear. We discovered that NudC is an essential transfer factor with an unprecedented mode of action: NudC interacts with Hsp40 in Hsp40-Hsp70-client complexes and displaces Hsp70. Then, the interaction of NudC with Hsp90 allows the direct transfer of Hsp40-bound clients to Hsp90 for further processing. Consistent with this mechanism, NudC increases client activation in vitro as well as in cells and is essential for cellular viability. Together, our results show the complexity of the cooperation between the major chaperone machineries in the eukaryotic cytosol.<br />Competing Interests: Declaration of interests The authors declare no competing interests.<br /> (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)