The cochaperone CHIP marks Hsp70- and Hsp90-bound substrates for degradation through a very flexible mechanism

© The Author(s) 2019.

Detalles Bibliográficos
Autores: Quintana-Gallardo, Lucía, Martín-Benito, Jaime, Marcilla, Miguel, Espadas, Guadalupe, Sabidó, Eduard, Valpuesta, José M.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2019
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/241321
Acceso en línea:http://hdl.handle.net/10261/241321
Access Level:acceso abierto
Palabra clave:Chaperones
Cryoelectron microscopy
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spelling The cochaperone CHIP marks Hsp70- and Hsp90-bound substrates for degradation through a very flexible mechanismQuintana-Gallardo, LucíaMartín-Benito, JaimeMarcilla, MiguelEspadas, GuadalupeSabidó, EduardValpuesta, José M.ChaperonesCryoelectron microscopy© The Author(s) 2019.Some molecular chaperones are involved not only in assisting the folding of proteins but also, given appropriate conditions, in their degradation. This is the case for Hsp70 and Hsp90 which, in concert with the cochaperone CHIP, direct their bound substrate to degradation through ubiquitination. We generated complexes between the chaperones (Hsp70 or Hsp90), the cochaperone CHIP and, as substrate, a p53 variant containing the GST protein (p53-TMGST). Both ternary complexes (Hsp70:p53-TMGST:CHIP and Hsp90:p53-TMGST:CHIP) ubiquitinated the substrate at a higher efficiency than in the absence of the chaperones. The 3D structures of the two complexes, obtained using a combination of cryoelectron microscopy and crosslinking mass spectrometry, showed the substrate located between the chaperone and the cochaperone, suggesting a ubiquitination mechanism in which the chaperone-bound substrate is presented to CHIP. These complexes are inherently flexible, which is important for the ubiquitination process.This research was supported by the grant BFU2016-75984 (AEI/FEDER, EU) to JMV. We thank Diamond Light Source for access to beamline EM16943 and EM15997 that contributed to the results presented here. The CRG/UPF Proteomics Unit is a member of Proteored, PRB3 and is supported by grant PT17/0019, of the PE I + D + i 2013–2016, funded by ISCIII and ERDF. We acknowledge support from the Spanish Ministry of Economy and Competitiveness, “Centro de Excelencia Severo Ochoa 2013–2017”, SEV-2012–0208, and “Secretaria d’Universitats i Recerca del Departament d’Economia i Coneixement de la Generalitat de Catalunya” (2017SGR595).Springer NatureMinisterio de Economía y Competitividad (España)Diamond Light Source (UK)Instituto de Salud Carlos IIIGeneralitat de CatalunyaConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2021202120192021info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/241321reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/BFU2016-75984http://dx.doi.org/10.1038/s41598-019-41060-0Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/2413212026-05-22T06:33:51Z
dc.title.none.fl_str_mv The cochaperone CHIP marks Hsp70- and Hsp90-bound substrates for degradation through a very flexible mechanism
title The cochaperone CHIP marks Hsp70- and Hsp90-bound substrates for degradation through a very flexible mechanism
spellingShingle The cochaperone CHIP marks Hsp70- and Hsp90-bound substrates for degradation through a very flexible mechanism
Quintana-Gallardo, Lucía
Chaperones
Cryoelectron microscopy
title_short The cochaperone CHIP marks Hsp70- and Hsp90-bound substrates for degradation through a very flexible mechanism
title_full The cochaperone CHIP marks Hsp70- and Hsp90-bound substrates for degradation through a very flexible mechanism
title_fullStr The cochaperone CHIP marks Hsp70- and Hsp90-bound substrates for degradation through a very flexible mechanism
title_full_unstemmed The cochaperone CHIP marks Hsp70- and Hsp90-bound substrates for degradation through a very flexible mechanism
title_sort The cochaperone CHIP marks Hsp70- and Hsp90-bound substrates for degradation through a very flexible mechanism
dc.creator.none.fl_str_mv Quintana-Gallardo, Lucía
Martín-Benito, Jaime
Marcilla, Miguel
Espadas, Guadalupe
Sabidó, Eduard
Valpuesta, José M.
author Quintana-Gallardo, Lucía
author_facet Quintana-Gallardo, Lucía
Martín-Benito, Jaime
Marcilla, Miguel
Espadas, Guadalupe
Sabidó, Eduard
Valpuesta, José M.
author_role author
author2 Martín-Benito, Jaime
Marcilla, Miguel
Espadas, Guadalupe
Sabidó, Eduard
Valpuesta, José M.
author2_role author
author
author
author
author
dc.contributor.none.fl_str_mv Ministerio de Economía y Competitividad (España)
Diamond Light Source (UK)
Instituto de Salud Carlos III
Generalitat de Catalunya
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Chaperones
Cryoelectron microscopy
topic Chaperones
Cryoelectron microscopy
description © The Author(s) 2019.
publishDate 2019
dc.date.none.fl_str_mv 2019
2021
2021
2021
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/241321
url http://hdl.handle.net/10261/241321
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv #PLACEHOLDER_PARENT_METADATA_VALUE#
info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/BFU2016-75984
http://dx.doi.org/10.1038/s41598-019-41060-0
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Springer Nature
publisher.none.fl_str_mv Springer Nature
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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