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Cited by 25Cellular transport and secretionRNA and protein synthesis mechanismsEndoplasmic Reticulum Stress and Disease

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Molecular view of ER membrane remodeling by the Sec61/TRAP translocon

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Karki, Sudeep, Javanainen, Matti, Rehan, Shahid, Tranter, Dale, Kellosalo, Juho, Huiskonen, Juha T, Happonen, Lotta, Paavilainen, Ville·2023·The EMBO Reports
DOI 10.15252/embr.202357910PMC PMC10702806

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Abstract

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.

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Metadata

Authors
Karki, S., Javanainen, M., Rehan, S., Tranter, D., Kellosalo, J., Huiskonen, J. T., Happonen, L., & Paavilainen, V.
Affiliations
  • University of Helsinki (FI)
  • Lund University (SE)
Corresponding author
Paavilainen, Ville
ORCID
Venue
The EMBO Reports
Publisher
Springer Science and Business Media LLC
Published
2023-11-20
Volume
24
Issue
12
Pages
e57910-e57910
ISSN
  • 1469-221X (ISSN-L)
  • 1469-3178
DOI
10.15252/embr.202357910
PMC
PMC10702806
OpenAlex
W4388869319
Cited by
25
References
3
Citations by year
2026: 3 · 2025: 6 · 2024: 8 · 2023: 7
FWCI
3.47
Type
journal article
Language
en
Open access
Licence
Locations
  • EMBO Reports (publishedVersion, other-oa)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Työväentutkimus Vuosikirja (acceptedVersion)
  • Lund University Publications (Lund University) (submittedVersion, cc-by)
Funders
  • Academy of Finland (338836, 314672, 314669, 338160)
  • Jane and Aatos Erkko Foundation
  • Sigrid Juselius Foundation
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Endoplasmic Reticulum Stress and Disease
Keywords
Sec61, TRAP complex, protein translocation, ribosome exit tunnel, membrane curvature, secretory pathway
MeSH terms
SEC Translocation Channels, Animals, Calcium-Binding Proteins, Endoplasmic Reticulum, Mammals, Membrane Glycoproteins, Membrane Proteins, Peptides, Receptors, Peptide, Receptors, Cytoplasmic and Nuclear, Protein Transport

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