Hsp70 Forms Antiparallel Dimers Stabilized by Post-translational Modifications to Position Clients for Transfer to Hsp90

Nina Morgner; Carla Schmidt; Victoria Beilsten-Edmands; Ima-obong Ebong; Nisha A. Patel; Eugenia M. Clerico; Elaine Kirschke; Soumya Daturpalli; Sophie E. Jackson; David Agard; Carol V. Robinson

doi:10.1016/j.celrep.2015.03.063

Cell Reports (May 2015)

Hsp70 Forms Antiparallel Dimers Stabilized by Post-translational Modifications to Position Clients for Transfer to Hsp90

Nina Morgner,
Carla Schmidt,
Victoria Beilsten-Edmands,
Ima-obong Ebong,
Nisha A. Patel,
Eugenia M. Clerico,
Elaine Kirschke,
Soumya Daturpalli,
Sophie E. Jackson,
David Agard,
Carol V. Robinson

Affiliations

Nina Morgner: Department of Chemistry, University of Oxford, South Parks Road, Oxford OX1 3QZ, UK
Carla Schmidt: Department of Chemistry, University of Oxford, South Parks Road, Oxford OX1 3QZ, UK
Victoria Beilsten-Edmands: Department of Chemistry, University of Oxford, South Parks Road, Oxford OX1 3QZ, UK
Ima-obong Ebong: Department of Chemistry, University of Oxford, South Parks Road, Oxford OX1 3QZ, UK
Nisha A. Patel: Department of Chemistry, University of Oxford, South Parks Road, Oxford OX1 3QZ, UK
Eugenia M. Clerico: Department of Biochemistry and Molecular Biology, University of Massachusetts, Amherst, MA 01003, USA
Elaine Kirschke: Department of Biochemistry and Biophysics, Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94158, USA
Soumya Daturpalli: Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK
Sophie E. Jackson: Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK
David Agard: Department of Biochemistry and Biophysics, Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94158, USA
Carol V. Robinson: Department of Chemistry, University of Oxford, South Parks Road, Oxford OX1 3QZ, UK

DOI: https://doi.org/10.1016/j.celrep.2015.03.063
Journal volume & issue: Vol. 11, no. 5
pp. 759 – 769

Abstract

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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.

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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