Structural analysis of the dynamic ribosome-translocon complex
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Abstract
The protein translocon at the endoplasmic reticulum comprises the Sec61 translocation channel and numerous accessory factors that collectively facilitate the biogenesis of secretory and membrane proteins. Here, we leveraged recent advances in cryo-electron microscopy (cryo-EM) and structure prediction to derive insights into several novel configurations of the ribosome-translocon complex. We show how a transmembrane domain (TMD) in a looped configuration passes through the Sec61 lateral gate during membrane insertion; how a nascent chain can bind and constrain the conformation of ribosomal protein uL22; and how the translocon-associated protein (TRAP) complex can adjust its position during different stages of protein biogenesis. Most unexpectedly, we find that a large proportion of translocon complexes contains RAMP4 intercalated into Sec61’s lateral gate, widening Sec61’s central pore and contributing to its hydrophilic interior. These structures lead to mechanistic hypotheses for translocon function and highlight a remarkably plastic machinery whose conformations and composition adjust dynamically to its diverse range of substrates.
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Flagged first, then by citations
- Authors
- Lewis, A. J., Zhong, F., Keenan, R. J., & Hegde, R. S.
- Affiliations
- MRC Laboratory of Molecular Biology (GB)
- University of Chicago (US)
- Corresponding author
- Hegde, Ramanujan S
- Venue
- eLife
- Publisher
- eLife Sciences Publications, Ltd
- Published
- 2024-06-18
- Volume
- 13
- ISSN
- 2050-084X (ISSN-L)
- OpenAlex
- W4399804388
- Cited by
- 9
- References
- 7
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 1
- FWCI
- 1.23
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- eLife (publishedVersion, cc-by)
- Knowledge@UChicago (University of Chicago) (submittedVersion, cc-by-nc-nd)
- Funders
- Medical Research Council (MC_UP_A022_1007)
- National Institutes of Health (R35 GM145374, T32 GM007183)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Structural Biology › Advanced Electron Microscopy Techniques and Applications
- Keywords
- nascent polypeptide chains, membrane protein insertion, membrane protein biogenesis
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