Structural analysis of the dynamic ribosome-translocon complex
Open accessPublished version of a preprint
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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Highly accurate protein structure prediction with AlphaFold
Jumper, J., Evans, R., Pritzel, A., Green, T., Figurnov, M., Ronneberger, O., Tunyasuvunakool, K., Bates, R., Žídek, A., Potapenko, A., et al. (2021) · Nature · doi:10.1038/s41586-021-03819-2 · Cited by 43,764 · see citing works
Protein complex prediction with AlphaFold-Multimer
Evans, R., O’Neill, M., Pritzel, A., Antropova, N., Senior, A., Green, T., Žídek, A., Bates, R., Blackwell, S., Yim, J., et al. (2021) · doi:10.1101/2021.10.04.463034 · Cited by 3,808 · see citing works
Highly accurate protein structure prediction for the human proteome
Tunyasuvunakool, K., Adler, J., Wu, Z., Green, T., Zielinski, M., Žídek, A., Bridgland, A., Cowie, A., Meyer, C., Laydon, A., et al. (2021) · Nature · doi:10.1038/s41586-021-03828-1 · Cited by 3,025 · see citing works
Fast and accurate protein structure search with Foldseek
van Kempen, M., Kim, S. S., Tumescheit, C., Mirdita, M., Lee, J., Gilchrist, C. L. M., Söding, J., & Steinegger, M. (2022) · doi:10.1101/2022.02.07.479398 · Cited by 2,598 · see citing works
Fast and accurate protein structure search with Foldseek
van Kempen, M., Kim, S. S., Tumescheit, C., Mirdita, M., Lee, J., Gilchrist, C. L. M., Söding, J., & Steinegger, M. (2024) · Nature Biotechnology · doi:10.1038/s41587-023-01773-0 · Cited by 2,596 · see citing works
Varadi, M., Bertoni, D., Magana, P., Paramval, U., Pidruchna, I., Radhakrishnan, M., Tsenkov, M., Nair, S., Mirdita, M., Yeo, J., et al. (2024) · Nucleic Acids Research · doi:10.1093/nar/gkad1011 · Cited by 2,052 · see citing works
Structure of a complex of the ATPase SecA and the protein-translocation channel.
Zimmer, J., Nam, Y., & Rapoport, T. A. (2008) · Nature · doi:10.1038/nature07335 · Cited by 459 · see citing works
Cryo-EM structure of the ribosome-SecYE complex in the membrane environment.
Frauenfeld, J., Gumbart, J., Sluis, E. O. V. D., Funes, S., Gartmann, M., Beatrix, B., Mielke, T., Berninghausen, O., Becker, T., Schulten, K., et al. (2011) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.2026 · Cited by 298 · see citing works
A genome-wide atlas of co-essential modules assigns function to uncharacterized genes
Wainberg, M., Kamber, R. A., Balsubramani, A., Meyers, R. M., Sinnott-Armstrong, N., Hornburg, D., Jiang, L., Chan, J., Jian, R., Gu, M., et al. (2021) · Nature Genetics · doi:10.1038/s41588-021-00840-z · Cited by 204 · see citing works
Structures of the E. coli translating ribosome with SRP and its receptor and with the translocon
Jomaa, A., Boehringer, D., Leibundgut, M., & Ban, N. (2016) · Nature Communications · doi:10.1038/ncomms10471 · Cited by 115 · see citing works
YidC and SecYEG form a heterotetrameric protein translocation channel.
Sachelaru, I., Winter, L., Knyazev, D. G., Zimmermann, M., Vogt, A., Kuttner, R., Ollinger, N., Siligan, C., Pohl, P., & Koch, H.-G. (2017) · Scientific Reports · doi:10.1038/s41598-017-00109-8 · Cited by 58 · see citing works
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)
- PMC
- PMC11186639
- OpenAlex
- W4394856497
- Cited by
- 11
- References
- 11
- Citations by year
- 2026: 7 · 2025: 3 · 2024: 1
- FWCI
- 1.50
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- eLife (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- 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
- membrane protein biogenesis
- MeSH terms
- SEC Translocation Channels, Endoplasmic Reticulum, Humans, Membrane Proteins, Models, Molecular, Protein Conformation, Ribosomal Proteins, Ribosomes, Cryoelectron Microscopy, Protein Transport
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