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Cell Rep. 2015 May 5;11(5):759-69. doi: 10.1016/j.celrep.2015.03.063. Epub 2015 Apr 23.

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

Author information

1
Department of Chemistry, University of Oxford, South Parks Road, Oxford OX1 3QZ, UK. Electronic address: morgner@chemie.uni-frankfurt.de.
2
Department of Chemistry, University of Oxford, South Parks Road, Oxford OX1 3QZ, UK.
3
Department of Biochemistry and Molecular Biology, University of Massachusetts, Amherst, MA 01003, USA.
4
Department of Biochemistry and Biophysics, Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94158, USA.
5
Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK.
6
Department of Chemistry, University of Oxford, South Parks Road, Oxford OX1 3QZ, UK. Electronic address: carol.robinson@chem.ox.ac.uk.

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.

PMID:
25921532
PMCID:
PMC4431665
DOI:
10.1016/j.celrep.2015.03.063
[Indexed for MEDLINE]
Free PMC Article

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