Hsp70 Forms Antiparallel Dimers Stabilized by Post-translational Modifications to Position Clients for Transfer to Hsp90
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 m...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2015-05-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S221112471500354X |
| _version_ | 1811306123613962240 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Nina Morgner |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-13T08:38:47Z |
| format | Article |
| id | doaj.art-44cbb207b5e1483da5af592660e5f1ce |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-04-13T08:38:47Z |
| publishDate | 2015-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-44cbb207b5e1483da5af592660e5f1ce2022-12-22T02:53:59ZengElsevierCell Reports2211-12472015-05-0111575976910.1016/j.celrep.2015.03.063Hsp70 Forms Antiparallel Dimers Stabilized by Post-translational Modifications to Position Clients for Transfer to Hsp90Nina Morgner0Carla Schmidt1Victoria Beilsten-Edmands2Ima-obong Ebong3Nisha A. Patel4Eugenia M. Clerico5Elaine Kirschke6Soumya Daturpalli7Sophie E. Jackson8David Agard9Carol V. Robinson10Department of Chemistry, University of Oxford, South Parks Road, Oxford OX1 3QZ, UKDepartment of Chemistry, University of Oxford, South Parks Road, Oxford OX1 3QZ, UKDepartment of Chemistry, University of Oxford, South Parks Road, Oxford OX1 3QZ, UKDepartment of Chemistry, University of Oxford, South Parks Road, Oxford OX1 3QZ, UKDepartment of Chemistry, University of Oxford, South Parks Road, Oxford OX1 3QZ, UKDepartment of Biochemistry and Molecular Biology, University of Massachusetts, Amherst, MA 01003, USADepartment of Biochemistry and Biophysics, Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94158, USADepartment of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UKDepartment of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UKDepartment of Biochemistry and Biophysics, Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94158, USADepartment of Chemistry, University of Oxford, South Parks Road, Oxford OX1 3QZ, UKProtein 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.http://www.sciencedirect.com/science/article/pii/S221112471500354X |
| spellingShingle | 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 Hsp70 Forms Antiparallel Dimers Stabilized by Post-translational Modifications to Position Clients for Transfer to Hsp90 Cell Reports |
| title | Hsp70 Forms Antiparallel Dimers Stabilized by Post-translational Modifications to Position Clients for Transfer to Hsp90 |
| title_full | Hsp70 Forms Antiparallel Dimers Stabilized by Post-translational Modifications to Position Clients for Transfer to Hsp90 |
| title_fullStr | Hsp70 Forms Antiparallel Dimers Stabilized by Post-translational Modifications to Position Clients for Transfer to Hsp90 |
| title_full_unstemmed | Hsp70 Forms Antiparallel Dimers Stabilized by Post-translational Modifications to Position Clients for Transfer to Hsp90 |
| title_short | Hsp70 Forms Antiparallel Dimers Stabilized by Post-translational Modifications to Position Clients for Transfer to Hsp90 |
| title_sort | hsp70 forms antiparallel dimers stabilized by post translational modifications to position clients for transfer to hsp90 |
| url | http://www.sciencedirect.com/science/article/pii/S221112471500354X |
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