Structure of the SecY channel during initiation of protein translocation
Open accessAbstract
Many secretory proteins are targeted by signal sequences to a protein-conducting channel, formed by prokaryotic SecY or eukaryotic Sec61 complexes, and are translocated across the membrane during their synthesis. Crystal structures of the inactive channel show that the SecY subunit of the heterotrimeric complex consists of two halves that form an hourglass-shaped pore with a constriction in the middle of the membrane and a lateral gate that faces the lipid phase. The closed channel has an empty cytoplasmic funnel and an extracellular funnel that is filled with a small helical domain, called the plug. During initiation of translocation, a ribosome-nascent chain complex binds to the SecY (or Sec61) complex, resulting in insertion of the nascent chain. However, the mechanism of channel opening during translocation is unclear. Here we have addressed this question by determining structures of inactive and active ribosome-channel complexes with cryo-electron microscopy. Non-translating ribosome-SecY channel complexes derived from Methanocaldococcus jannaschii or Escherichia coli show the channel in its closed state, and indicate that ribosome binding per se causes only minor changes. The structure of an active E. coli ribosome-channel complex demonstrates that the nascent chain opens the channel, causing mostly rigid body movements of the amino- and carboxy-terminal halves of SecY. In this early translocation intermediate, the polypeptide inserts as a loop into the SecY channel with the hydrophobic signal sequence intercalated into the open lateral gate. The nascent chain also forms a loop on the cytoplasmic surface of SecY rather than entering the channel directly.
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- Authors
- Park, E., Ménétret, J.-F., Gumbart, J. C., Ludtke, S. J., Li, W., Whynot, A., Rapoport, T. A., & Akey, C. W.
- Affiliations
- Howard Hughes Medical Institute (US)
- Boston University (US)
- Georgia Institute of Technology (US)
- Baylor College of Medicine (US)
- Corresponding author
- Rapoport, Tom A.
- Akey, Christopher W.
- Venue
- Nature
- Published
- 2013-10-23
- Volume
- 506
- Issue
- 7486
- Pages
- 102-106
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC3948209
- OpenAlex
- W2171679939
- Cited by
- 148
- References
- 40
- Citations by year
- 2026: 4 · 2025: 2 · 2024: 4 · 2023: 3 · 2022: 10 · 2021: 9 · 2020: 8 · 2019: 14 · 2018: 13 · 2017: 12 · 2016: 24 · 2015: 24 · 2014: 21
- FWCI
- 10.24
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- Howard Hughes Medical Institute
- National Heart, Lung, and Blood Institute (K99HL097083, R00HL097083, R01HL121718)
- National Institute of General Medical Sciences (GM067887, GM45377, R01GM045377, GM052586, R01GM080139, R01GM067887, GM080139, R01GM052586)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Keywords
- Sec61, protein translocation, nascent chain, signal peptide, ribosome binding, Methanococcus jannaschii, Escherichia coli, ribosome recycling factor, translocation intermediates, membrane protein targeting
- MeSH terms
- SEC Translocation Channels, Escherichia coli, Models, Molecular, Peptides, Protein Binding, Ribosomes, Protein Biosynthesis, Ultrasonography, Cryoelectron Microscopy, Protein Subunits, Protein Transport, Escherichia coli Proteins, Multiprotein Complexes, Methanocaldococcus
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