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

被引:18
|
作者
Biebl, Maximilian M. [1 ]
Delhommel, Florent [1 ,2 ]
Faust, Ofrah [3 ]
Zak, Krzysztof M. [2 ]
Agam, Ganesh [4 ]
Guo, Xiaoyan [5 ,6 ]
Muehlhofer, Moritz [1 ]
Dahiya, Vinay [1 ]
Hillebrand, Daniela [1 ]
Popowicz, Grzegorz M. [2 ]
Kampmann, Martin [5 ,6 ]
Lamb, Don C. [4 ]
Rosenzweig, Rina [3 ]
Sattler, Michael [1 ,2 ]
Buchner, Johannes [1 ]
机构
[1] Tech Univ Munich, Dept Chem, Lichtenbergstr 4, D-85747 Garching, Germany
[2] Helmholtz Zentrum Munchen, Inst Biol Struct, Neuherberg, Germany
[3] Weizmann Inst Sci, Dept Biol Struct, Rehovot, Israel
[4] Ludwig Maximilians Univ Munchen, Dept Chem, Munich, Germany
[5] Univ Calif San Francisco, Inst Neurodegenerat Dis, San Francisco, CA 94143 USA
[6] Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA USA
基金
欧洲研究理事会;
关键词
NMR-SPECTROSCOPY; STRUCTURAL-CHARACTERIZATION; PROTEIN; HSP70; BINDING; P53; ARCHITECTURE; REVEALS; ATPASE; CRISPR;
D O I
10.1016/j.molcel.2021.12.031
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:555 / +
页数:23
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