Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

Protein folding in cells is regulated by networks of chaperones, including the heat shock protein 70 (Hsp70) system, which consists of the Hsp40 cochaperone and a nucleotide exchange factor. Hsp40 mediates complex formation between Hsp70 and client proteins prior to interaction with Hsp90. We used mass spectrometry (MS) to monitor assemblies formed between eukaryotic Hsp90/Hsp70/Hsp40, Hop, p23, and a client protein, a fragment of the glucocorticoid receptor (GR). We found that Hsp40 promotes interactions between the client and Hsp70, and facilitates dimerization of monomeric Hsp70. This dimerization is antiparallel, stabilized by post-translational modifications (PTMs), and maintained in the stable heterohexameric client-loading complex Hsp902Hsp702HopGR identified here. Addition of p23 to this client-loading complex induces transfer of GR onto Hsp90 and leads to expulsion of Hop and Hsp70. Based on these results, we propose that Hsp70 antiparallel dimerization, stabilized by PTMs, positions the client for transfer from Hsp70 to Hsp90.

Original publication

DOI

10.1016/j.celrep.2015.03.063

Type

Journal article

Journal

Cell Rep

Publication Date

05/05/2015

Volume

11

Pages

759 - 769

Keywords

Dimerization, Escherichia coli, HSP40 Heat-Shock Proteins, HSP70 Heat-Shock Proteins, HSP90 Heat-Shock Proteins, Humans, Protein Binding, Protein Folding, Protein Multimerization, Protein Processing, Post-Translational, Protein Structure, Secondary, Protein Structure, Tertiary, Receptors, Glucocorticoid, Recombinant Proteins, Saccharomyces cerevisiae Proteins