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Hsp70 forms antiparallel dimers stabilized by post-translational modifications to position clients for transfer to Hsp90.


ABSTRACT: 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.

SUBMITTER: Morgner N 

PROVIDER: S-EPMC4431665 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature

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Hsp70 forms antiparallel dimers stabilized by post-translational modifications to position clients for transfer to Hsp90.

Morgner Nina N   Schmidt Carla C   Beilsten-Edmands Victoria V   Ebong Ima-Obong IO   Patel Nisha A NA   Clerico Eugenia M EM   Kirschke Elaine E   Daturpalli Soumya S   Jackson Sophie E SE   Agard David D   Robinson Carol V CV  

Cell reports 20150423 5


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 in  ...[more]

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