Structure of Hsp90-Hsp70-Hop-GR reveals the Hsp90 client-loading mechanism.

ABSTRACT: Maintaining a healthy proteome is fundamental for the survival of all organisms¹. Integral to this are Hsp90 and Hsp70, molecular chaperones that together facilitate the folding, remodelling and maturation of the many 'client proteins' of Hsp90². The glucocorticoid receptor (GR) is a model client protein that is strictly dependent on Hsp90 and Hsp70 for activity^3-7. Chaperoning GR involves a cycle of inactivation by Hsp70; formation of an inactive GR-Hsp90-Hsp70-Hop 'loading' complex; conversion to an active GR-Hsp90-p23 'maturation' complex; and subsequent GR release⁸. However, to our knowledge, a molecular understanding of this intricate chaperone cycle is lacking for any client protein. Here we report the cryo-electron microscopy structure of

SUBMITTER: Wang RY 

PROVIDER: S-EPMC9179170 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature