A switch from α-helical to β-strand conformation during co-translational protein folding

Cellular proteins begin to fold as they emerge from the ribosome. The folding landscape of nascent chains is not only shaped by their amino acid sequence but also by the interactions with the ribosome. Here, we combine biophysical methods with cryo-EM structure determination to show that folding of...

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Autores: Agirrezabala, Xabier, Samatoba, Ekaterina, Macher, Meline, Liutkute, Marija, Maiti, Manisankar, Gil-Cartón, David, Nováček, Jiří, Valle, Mikel, Rodnina, Marina V.
Formato: artículo
Fecha de publicación:2022
País:España
Recursos:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/296770
Acesso em linha:http://hdl.handle.net/10261/296770
Access Level:acceso abierto
Palavra-chave:Cotranslational folding
Nascent chain
Ribosome
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spelling A switch from α-helical to β-strand conformation during co-translational protein foldingAgirrezabala, XabierSamatoba, EkaterinaMacher, MelineLiutkute, MarijaMaiti, ManisankarGil-Cartón, DavidNováček, JiříValle, MikelRodnina, Marina V.Cotranslational foldingNascent chainRibosomeCellular proteins begin to fold as they emerge from the ribosome. The folding landscape of nascent chains is not only shaped by their amino acid sequence but also by the interactions with the ribosome. Here, we combine biophysical methods with cryo-EM structure determination to show that folding of a β-barrel protein begins with formation of a dynamic α-helix inside the ribosome. As the growing peptide reaches the end of the tunnel, the N-terminal part of the nascent chain refolds to a β-hairpin structure that remains dynamic until its release from the ribosome. Contacts with the ribosome and structure of the peptidyl transferase center depend on nascent chain conformation. These results indicate that proteins may start out as α-helices inside the tunnel and switch into their native folds only as they emerge from the ribosome. Moreover, the correlation of nascent chain conformations with reorientation of key residues of the ribosomal peptidyl-transferase center suggest that protein folding could modulate ribosome activity.The work was funded by the Max Planck Society to M.V.R., the European Research Council (ERC) Advanced Investigator Grant RIBOFOLD to M.V.R. (proposal number n° 787926), and the Spanish Ministry of Economy and Competitiveness to X.A. (CTQ2015-73560-JIN) and to M.V. (PGC2018-098996-B-I00). We thank the Spanish Ministry of Science for the Severo Ochoa Excellence Accreditations to the CIC bioGUNE (SEV-2016-0644). CIISB research infrastructure project LM2018127 funded by MEYS CR is gratefully acknowledged for the financial support of the measurements at the CF Cryo-electron Microscopy and Tomography. Open Access funding enabled and organized by Projekt DEAL.Peer reviewedEMBO PressMax Planck SocietyEuropean Research CouncilMinisterio de Economía y Competitividad (España)Ministerio de Ciencia, Innovación y Universidades (España)Agencia Estatal de Investigación (España)Ministry of Education, Youth and Sports (Czech Republic)German Rectors' ConferenceConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202320232022info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501application/pdfhttp://hdl.handle.net/10261/296770reponame: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#info:eu-repo/grantAgreement/MINECO//CTQ2015-73560-JINinfo:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PGC2018-098996-B-I00info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SEV-2016-0644The underlying dataset has been published as supplementary material of the article in the publisher platform at 10.15252/embj.2021109175https://doi.org/10.15252/embj.2021109175Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/2967702026-05-22T06:33:51Z
dc.title.none.fl_str_mv A switch from α-helical to β-strand conformation during co-translational protein folding
title A switch from α-helical to β-strand conformation during co-translational protein folding
spellingShingle A switch from α-helical to β-strand conformation during co-translational protein folding
Agirrezabala, Xabier
Cotranslational folding
Nascent chain
Ribosome
title_short A switch from α-helical to β-strand conformation during co-translational protein folding
title_full A switch from α-helical to β-strand conformation during co-translational protein folding
title_fullStr A switch from α-helical to β-strand conformation during co-translational protein folding
title_full_unstemmed A switch from α-helical to β-strand conformation during co-translational protein folding
title_sort A switch from α-helical to β-strand conformation during co-translational protein folding
dc.creator.none.fl_str_mv Agirrezabala, Xabier
Samatoba, Ekaterina
Macher, Meline
Liutkute, Marija
Maiti, Manisankar
Gil-Cartón, David
Nováček, Jiří
Valle, Mikel
Rodnina, Marina V.
author Agirrezabala, Xabier
author_facet Agirrezabala, Xabier
Samatoba, Ekaterina
Macher, Meline
Liutkute, Marija
Maiti, Manisankar
Gil-Cartón, David
Nováček, Jiří
Valle, Mikel
Rodnina, Marina V.
author_role author
author2 Samatoba, Ekaterina
Macher, Meline
Liutkute, Marija
Maiti, Manisankar
Gil-Cartón, David
Nováček, Jiří
Valle, Mikel
Rodnina, Marina V.
author2_role author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Max Planck Society
European Research Council
Ministerio de Economía y Competitividad (España)
Ministerio de Ciencia, Innovación y Universidades (España)
Agencia Estatal de Investigación (España)
Ministry of Education, Youth and Sports (Czech Republic)
German Rectors' Conference
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Cotranslational folding
Nascent chain
Ribosome
topic Cotranslational folding
Nascent chain
Ribosome
description Cellular proteins begin to fold as they emerge from the ribosome. The folding landscape of nascent chains is not only shaped by their amino acid sequence but also by the interactions with the ribosome. Here, we combine biophysical methods with cryo-EM structure determination to show that folding of a β-barrel protein begins with formation of a dynamic α-helix inside the ribosome. As the growing peptide reaches the end of the tunnel, the N-terminal part of the nascent chain refolds to a β-hairpin structure that remains dynamic until its release from the ribosome. Contacts with the ribosome and structure of the peptidyl transferase center depend on nascent chain conformation. These results indicate that proteins may start out as α-helices inside the tunnel and switch into their native folds only as they emerge from the ribosome. Moreover, the correlation of nascent chain conformations with reorientation of key residues of the ribosomal peptidyl-transferase center suggest that protein folding could modulate ribosome activity.
publishDate 2022
dc.date.none.fl_str_mv 2022
2023
2023
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/296770
url http://hdl.handle.net/10261/296770
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#
info:eu-repo/grantAgreement/MINECO//CTQ2015-73560-JIN
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PGC2018-098996-B-I00
info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SEV-2016-0644
The underlying dataset has been published as supplementary material of the article in the publisher platform at 10.15252/embj.2021109175
https://doi.org/10.15252/embj.2021109175
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 EMBO Press
publisher.none.fl_str_mv EMBO Press
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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score 15,812429

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