The self-association equilibrium of DNAJA2 regulates its interaction with unfolded substrate proteins and with Hsc70

J-domain proteins tune the specificity of Hsp70s, engaging them in precise functions. Despite their essential role, the structure and function of many J-domain proteins remain largely unknown. We explore human DNAJA2, finding that it reversibly forms highly-ordered, tubular structures that can be di...

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Autores: Velasco-Carneros, Lorea, Cuéllar, Jorge, Dublang, Leire, Santiago, César, Maréchal, Jean Didier, Martín-Benito, Jaime, Maestro, Moisés, Fernández-Higuero, José Ángel, Orozco, Natalia, Moro, Fernando, Valpuesta, José M., Muga, Arturo
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2023
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/343998
Acceso en línea:http://hdl.handle.net/10261/343998
Access Level:acceso abierto
Palabra clave:Chaperones
Cryoelectron microscopy
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spelling The self-association equilibrium of DNAJA2 regulates its interaction with unfolded substrate proteins and with Hsc70Velasco-Carneros, LoreaCuéllar, JorgeDublang, LeireSantiago, CésarMaréchal, Jean DidierMartín-Benito, JaimeMaestro, MoisésFernández-Higuero, José ÁngelOrozco, NataliaMoro, FernandoValpuesta, José M.Muga, ArturoChaperonesCryoelectron microscopyJ-domain proteins tune the specificity of Hsp70s, engaging them in precise functions. Despite their essential role, the structure and function of many J-domain proteins remain largely unknown. We explore human DNAJA2, finding that it reversibly forms highly-ordered, tubular structures that can be dissociated by Hsc70, the constitutively expressed Hsp70 isoform. Cryoelectron microscopy and mutational studies reveal that different domains are involved in self-association. Oligomer dissociation into dimers potentiates its interaction with unfolded client proteins. The J-domains are accessible to Hsc70 within the tubular structure. They allow binding of closely spaced Hsc70 molecules that could be transferred to the unfolded substrate for its cooperative remodelling, explaining the efficient recovery of DNAJA2-bound clients. The disordered C-terminal domain, comprising the last 52 residues, regulates its holding activity and productive interaction with Hsc70. These in vitro findings suggest that the association equilibrium of DNAJA2 could regulate its interaction with client proteins and Hsc70.This research was supported by grants PID2019-111068GB-I00 (AEI/FEDER, UE) to A.M., PID2020-117752RB-I00 (AEI/FEDER, UE) to J.M.B., and PID2019-105872GB-I00 and PID2022-137175NB-I00 (AEI/FEDER, UE) to J.M.V. and J.C., and by the Basque Government (grants IT1201-19 and IT1745-22 to F.M.).Peer reviewedNature Publishing GroupMinisterio de Ciencia, Innovación y Universidades (España)Agencia Estatal de Investigación (España)European CommissionMinisterio de Ciencia e Innovación (España)Eusko JaurlaritzaConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202420242023info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://hdl.handle.net/10261/343998reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2019-111068GB-I00info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2020-117752RB-I00info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2019-105872GB-I00info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/PID2022-137175NB-I00Velasco-Carneros, Lorea ; Cuéllar, Jorge ; Dublang, Leire ; Santiago, César ; Maréchal, Jean Didier ; Martín-Benito, Jaime ; Maestro, Moisés ; Fernández-Higuero, José Ángel ; Orozco, Natalia ; Moro, Fernando ; Valpuesta, José M. ; Muga, Arturo; 2023; "Supplementary information: The self-association equilibrium of DNAJA2 regulates its interaction with unfolded substrate proteins and with Hsc70 [Dataset]"; Nature Publishing Group; https://doi.org/10.1038/s41467-023-41150-8https://doi.org/10.1038/s41467-023-41150-8Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/3439982026-05-22T06:33:51Z
dc.title.none.fl_str_mv The self-association equilibrium of DNAJA2 regulates its interaction with unfolded substrate proteins and with Hsc70
title The self-association equilibrium of DNAJA2 regulates its interaction with unfolded substrate proteins and with Hsc70
spellingShingle The self-association equilibrium of DNAJA2 regulates its interaction with unfolded substrate proteins and with Hsc70
Velasco-Carneros, Lorea
Chaperones
Cryoelectron microscopy
title_short The self-association equilibrium of DNAJA2 regulates its interaction with unfolded substrate proteins and with Hsc70
title_full The self-association equilibrium of DNAJA2 regulates its interaction with unfolded substrate proteins and with Hsc70
title_fullStr The self-association equilibrium of DNAJA2 regulates its interaction with unfolded substrate proteins and with Hsc70
title_full_unstemmed The self-association equilibrium of DNAJA2 regulates its interaction with unfolded substrate proteins and with Hsc70
title_sort The self-association equilibrium of DNAJA2 regulates its interaction with unfolded substrate proteins and with Hsc70
dc.creator.none.fl_str_mv Velasco-Carneros, Lorea
Cuéllar, Jorge
Dublang, Leire
Santiago, César
Maréchal, Jean Didier
Martín-Benito, Jaime
Maestro, Moisés
Fernández-Higuero, José Ángel
Orozco, Natalia
Moro, Fernando
Valpuesta, José M.
Muga, Arturo
author Velasco-Carneros, Lorea
author_facet Velasco-Carneros, Lorea
Cuéllar, Jorge
Dublang, Leire
Santiago, César
Maréchal, Jean Didier
Martín-Benito, Jaime
Maestro, Moisés
Fernández-Higuero, José Ángel
Orozco, Natalia
Moro, Fernando
Valpuesta, José M.
Muga, Arturo
author_role author
author2 Cuéllar, Jorge
Dublang, Leire
Santiago, César
Maréchal, Jean Didier
Martín-Benito, Jaime
Maestro, Moisés
Fernández-Higuero, José Ángel
Orozco, Natalia
Moro, Fernando
Valpuesta, José M.
Muga, Arturo
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Ministerio de Ciencia, Innovación y Universidades (España)
Agencia Estatal de Investigación (España)
European Commission
Ministerio de Ciencia e Innovación (España)
Eusko Jaurlaritza
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Chaperones
Cryoelectron microscopy
topic Chaperones
Cryoelectron microscopy
description J-domain proteins tune the specificity of Hsp70s, engaging them in precise functions. Despite their essential role, the structure and function of many J-domain proteins remain largely unknown. We explore human DNAJA2, finding that it reversibly forms highly-ordered, tubular structures that can be dissociated by Hsc70, the constitutively expressed Hsp70 isoform. Cryoelectron microscopy and mutational studies reveal that different domains are involved in self-association. Oligomer dissociation into dimers potentiates its interaction with unfolded client proteins. The J-domains are accessible to Hsc70 within the tubular structure. They allow binding of closely spaced Hsc70 molecules that could be transferred to the unfolded substrate for its cooperative remodelling, explaining the efficient recovery of DNAJA2-bound clients. The disordered C-terminal domain, comprising the last 52 residues, regulates its holding activity and productive interaction with Hsc70. These in vitro findings suggest that the association equilibrium of DNAJA2 could regulate its interaction with client proteins and Hsc70.
publishDate 2023
dc.date.none.fl_str_mv 2023
2024
2024
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/10261/343998
url http://hdl.handle.net/10261/343998
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv #PLACEHOLDER_PARENT_METADATA_VALUE#
#PLACEHOLDER_PARENT_METADATA_VALUE#
#PLACEHOLDER_PARENT_METADATA_VALUE#
#PLACEHOLDER_PARENT_METADATA_VALUE#
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2019-111068GB-I00
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2020-117752RB-I00
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2019-105872GB-I00
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/PID2022-137175NB-I00
Velasco-Carneros, Lorea ; Cuéllar, Jorge ; Dublang, Leire ; Santiago, César ; Maréchal, Jean Didier ; Martín-Benito, Jaime ; Maestro, Moisés ; Fernández-Higuero, José Ángel ; Orozco, Natalia ; Moro, Fernando ; Valpuesta, José M. ; Muga, Arturo; 2023; "Supplementary information: The self-association equilibrium of DNAJA2 regulates its interaction with unfolded substrate proteins and with Hsc70 [Dataset]"; Nature Publishing Group; https://doi.org/10.1038/s41467-023-41150-8
https://doi.org/10.1038/s41467-023-41150-8
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
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
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