Snapshots of actin and tubulin folding inside the TRiC chaperonin.
Journal
Nature structural & molecular biology
ISSN: 1545-9985
Titre abrégé: Nat Struct Mol Biol
Pays: United States
ID NLM: 101186374
Informations de publication
Date de publication:
05 2022
05 2022
Historique:
received:
07
03
2021
accepted:
01
03
2022
pubmed:
23
4
2022
medline:
20
5
2022
entrez:
22
4
2022
Statut:
ppublish
Résumé
The integrity of a cell's proteome depends on correct folding of polypeptides by chaperonins. The chaperonin TCP-1 ring complex (TRiC) acts as obligate folder for >10% of cytosolic proteins, including he cytoskeletal proteins actin and tubulin. Although its architecture and how it recognizes folding substrates are emerging from structural studies, the subsequent fate of substrates inside the TRiC chamber is not defined. We trapped endogenous human TRiC with substrates (actin, tubulin) and cochaperone (PhLP2A) at different folding stages, for structure determination by cryo-EM. The already-folded regions of client proteins are anchored at the chamber wall, positioning unstructured regions toward the central space to achieve their native fold. Substrates engage with different sections of the chamber during the folding cycle, coupled to TRiC open-and-close transitions. Further, the cochaperone PhLP2A modulates folding, acting as a molecular strut between substrate and TRiC chamber. Our structural snapshots piece together an emerging model of client protein folding within TRiC.
Identifiants
pubmed: 35449234
doi: 10.1038/s41594-022-00755-1
pii: 10.1038/s41594-022-00755-1
pmc: PMC9113939
doi:
Substances chimiques
Actins
0
Peptides
0
Tubulin
0
Chaperonin Containing TCP-1
EC 3.6.1.-
Chaperonins
EC 3.6.1.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
420-429Subventions
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_PC_17137
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 092809/Z/10/Z
Pays : United Kingdom
Informations de copyright
© 2022. The Author(s).
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