Structures of the Gβ-CCT and PhLP1-Gβ-CCT complexes reveal a mechanism for G-protein β-subunit folding and Gβγ dimer assembly

G-protein signaling depends on the ability of the individual subunits of the G-protein heterotrimer to assemble into a functional complex. Formation of the G-protein βγ (Gβγ) dimer is particularly challenging because it is an obligate dimer in which the individual subunits are unstable on their own....

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Detalhes bibliográficos
Autores: Plimpton, Rebecca L, Cuéllar, Jorge, Lai, Chun Wan J, Aoba, Takuma, Makaju, Aman, Franklin, Sarah, Mathis, Andrew D, Prince, John T, Carrascosa, José L, Valpuesta, José M., Willardson, Barry M
Tipo de documento: artigo
Data de publicação:2015
País:España
Recursos:Consejo Superior de Investigaciones Científicas (CSIC)
Repositório:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/377378
Acesso em linha:http://hdl.handle.net/10261/377378
https://api.elsevier.com/content/abstract/scopus_id/84923657460
Access Level:Acceso aberto
Palavra-chave:G-protein
chaperonin
cross-linking
electron cryo-microscopy
phosducin-like protein
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repository_id_str
spelling Structures of the Gβ-CCT and PhLP1-Gβ-CCT complexes reveal a mechanism for G-protein β-subunit folding and Gβγ dimer assemblyPlimpton, Rebecca LCuéllar, JorgeLai, Chun Wan JAoba, TakumaMakaju, AmanFranklin, SarahMathis, Andrew DPrince, John TCarrascosa, José LValpuesta, José M.Willardson, Barry MG-proteinchaperonincross-linkingelectron cryo-microscopyphosducin-like proteinG-protein signaling depends on the ability of the individual subunits of the G-protein heterotrimer to assemble into a functional complex. Formation of the G-protein βγ (Gβγ) dimer is particularly challenging because it is an obligate dimer in which the individual subunits are unstable on their own. Recent studies have revealed an intricate chaperone system that brings Gβ and Gγ together. This system includes cytosolic chaperonin containing TCP-1 (CCT; also called TRiC) and its cochaperone phosducin-like protein 1 (PhLP1). Two key intermediates in the Gβγ assembly process, the Gβ-CCT and the PhLP1-Gβ-CCT complexes, were isolated and analyzed by a hybrid structural approach using cryo-electron microscopy, chemical cross-linking coupled with mass spectrometry, and unnatural amino acid cross-linking. The structures show that Gβ interacts with CCT in a near-native state through interactions of the Gγ-binding region of Gβ with the CCTγ subunit. PhLP1 binding stabilizes the Gβ fold, disrupting interactions with CCT and releasing a PhLP1-Gβ dimer for assembly with Gγ. This view provides unique insight into the interplay between CCT and a cochaperone to orchestrate the folding of a protein substrate.Peer reviewedConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202520252015info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501http://hdl.handle.net/10261/377378https://api.elsevier.com/content/abstract/scopus_id/84923657460reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)InglésProceedings of the National Academy of Sciences of the United States of Americahttps://doi.org/10.1073/pnas.1419595112Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/3773782026-05-22T06:33:51Z
dc.title.none.fl_str_mv Structures of the Gβ-CCT and PhLP1-Gβ-CCT complexes reveal a mechanism for G-protein β-subunit folding and Gβγ dimer assembly
title Structures of the Gβ-CCT and PhLP1-Gβ-CCT complexes reveal a mechanism for G-protein β-subunit folding and Gβγ dimer assembly
spellingShingle Structures of the Gβ-CCT and PhLP1-Gβ-CCT complexes reveal a mechanism for G-protein β-subunit folding and Gβγ dimer assembly
Plimpton, Rebecca L
G-protein
chaperonin
cross-linking
electron cryo-microscopy
phosducin-like protein
title_short Structures of the Gβ-CCT and PhLP1-Gβ-CCT complexes reveal a mechanism for G-protein β-subunit folding and Gβγ dimer assembly
title_full Structures of the Gβ-CCT and PhLP1-Gβ-CCT complexes reveal a mechanism for G-protein β-subunit folding and Gβγ dimer assembly
title_fullStr Structures of the Gβ-CCT and PhLP1-Gβ-CCT complexes reveal a mechanism for G-protein β-subunit folding and Gβγ dimer assembly
title_full_unstemmed Structures of the Gβ-CCT and PhLP1-Gβ-CCT complexes reveal a mechanism for G-protein β-subunit folding and Gβγ dimer assembly
title_sort Structures of the Gβ-CCT and PhLP1-Gβ-CCT complexes reveal a mechanism for G-protein β-subunit folding and Gβγ dimer assembly
dc.creator.none.fl_str_mv Plimpton, Rebecca L
Cuéllar, Jorge
Lai, Chun Wan J
Aoba, Takuma
Makaju, Aman
Franklin, Sarah
Mathis, Andrew D
Prince, John T
Carrascosa, José L
Valpuesta, José M.
Willardson, Barry M
author Plimpton, Rebecca L
author_facet Plimpton, Rebecca L
Cuéllar, Jorge
Lai, Chun Wan J
Aoba, Takuma
Makaju, Aman
Franklin, Sarah
Mathis, Andrew D
Prince, John T
Carrascosa, José L
Valpuesta, José M.
Willardson, Barry M
author_role author
author2 Cuéllar, Jorge
Lai, Chun Wan J
Aoba, Takuma
Makaju, Aman
Franklin, Sarah
Mathis, Andrew D
Prince, John T
Carrascosa, José L
Valpuesta, José M.
Willardson, Barry M
author2_role author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv G-protein
chaperonin
cross-linking
electron cryo-microscopy
phosducin-like protein
topic G-protein
chaperonin
cross-linking
electron cryo-microscopy
phosducin-like protein
description G-protein signaling depends on the ability of the individual subunits of the G-protein heterotrimer to assemble into a functional complex. Formation of the G-protein βγ (Gβγ) dimer is particularly challenging because it is an obligate dimer in which the individual subunits are unstable on their own. Recent studies have revealed an intricate chaperone system that brings Gβ and Gγ together. This system includes cytosolic chaperonin containing TCP-1 (CCT; also called TRiC) and its cochaperone phosducin-like protein 1 (PhLP1). Two key intermediates in the Gβγ assembly process, the Gβ-CCT and the PhLP1-Gβ-CCT complexes, were isolated and analyzed by a hybrid structural approach using cryo-electron microscopy, chemical cross-linking coupled with mass spectrometry, and unnatural amino acid cross-linking. The structures show that Gβ interacts with CCT in a near-native state through interactions of the Gγ-binding region of Gβ with the CCTγ subunit. PhLP1 binding stabilizes the Gβ fold, disrupting interactions with CCT and releasing a PhLP1-Gβ dimer for assembly with Gγ. This view provides unique insight into the interplay between CCT and a cochaperone to orchestrate the folding of a protein substrate.
publishDate 2015
dc.date.none.fl_str_mv 2015
2025
2025
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/10261/377378
https://api.elsevier.com/content/abstract/scopus_id/84923657460
url http://hdl.handle.net/10261/377378
https://api.elsevier.com/content/abstract/scopus_id/84923657460
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Proceedings of the National Academy of Sciences of the United States of America
https://doi.org/10.1073/pnas.1419595112
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
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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