Molecular view of ER membrane remodeling by the Sec61/TRAP translocon.
cryo-EM
membrane proteins
protein translocation
secretory proteins
structural biology
Journal
EMBO reports
ISSN: 1469-3178
Titre abrégé: EMBO Rep
Pays: England
ID NLM: 100963049
Informations de publication
Date de publication:
06 Dec 2023
06 Dec 2023
Historique:
revised:
27
10
2023
received:
01
08
2023
accepted:
01
11
2023
medline:
11
12
2023
pubmed:
20
11
2023
entrez:
20
11
2023
Statut:
ppublish
Résumé
Protein translocation across the endoplasmic reticulum (ER) membrane is an essential step during protein entry into the secretory pathway. The conserved Sec61 protein-conducting channel facilitates polypeptide translocation and coordinates cotranslational polypeptide-processing events. In cells, the majority of Sec61 is stably associated with a heterotetrameric membrane protein complex, the translocon-associated protein complex (TRAP), yet the mechanism by which TRAP assists in polypeptide translocation remains unknown. Here, we present the structure of the core Sec61/TRAP complex bound to a mammalian ribosome by cryogenic electron microscopy (cryo-EM). Ribosome interactions anchor the Sec61/TRAP complex in a conformation that renders the ER membrane locally thinner by significantly curving its lumenal leaflet. We propose that TRAP stabilizes the ribosome exit tunnel to assist nascent polypeptide insertion through Sec61 and provides a ratcheting mechanism into the ER lumen mediated by direct polypeptide interactions.
Identifiants
pubmed: 37983950
doi: 10.15252/embr.202357910
pmc: PMC10702806
doi:
Substances chimiques
signal sequence receptor
0
SEC Translocation Channels
0
Membrane Proteins
0
Peptides
0
Banques de données
PDB
['8BF9']
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e57910Subventions
Organisme : Academy of Finland (AKA)
ID : 338836
Organisme : Academy of Finland (AKA)
ID : 314672
Organisme : Academy of Finland (AKA)
ID : 314669
Organisme : Academy of Finland (AKA)
ID : 338160
Organisme : Jane and Aatos Erkko Foundation
Organisme : Sigrid Juselius Foundation
Informations de copyright
© 2023 The Authors. Published under the terms of the CC BY 4.0 license.
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