SecM-Stalled Ribosomes Adopt an Altered Geometry at the Peptidyl Transferase Center
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As nascent polypeptide chains are synthesized, they pass through a tunnel in the large ribosomal subunit. Interaction between specific nascent chains and the ribosomal tunnel is used to induce translational stalling for the regulation of gene expression. One well-characterized example is the Escherichia coli SecM (secretion monitor) gene product, which induces stalling to up-regulate translation initiation of the downstream secA gene, which is needed for protein export. Although many of the key components of SecM and the ribosomal tunnel have been identified, understanding of the mechanism by which the peptidyl transferase center of the ribosome is inactivated has been lacking. Here we present a cryo-electron microscopy reconstruction of a SecM-stalled ribosome nascent chain complex at 5.6 Å. While no cascade of rRNA conformational changes is evident, this structure reveals the direct interaction between critical residues of SecM and the ribosomal tunnel. Moreover, a shift in the position of the tRNA-nascent peptide linkage of the SecM-tRNA provides a rationale for peptidyl transferase center silencing, conditional on the simultaneous presence of a Pro-tRNA(Pro) in the ribosomal A-site. These results suggest a distinct allosteric mechanism of regulating translational elongation by the SecM stalling peptide.
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Loop III of TetM is less well-resolved than loops I and II, but additional electron density is clearly observable within the TetM•70S map and is absent in other cryo-EM maps lacking A-site ligands.
“Loop III of TetM linking β5 4 to helix αB 4 is less well-resolved than loops I and II, yet additional electron density is clearly observable within the TetM•70S map (Fig. 3C), which, in contrast, is absent in other cryo-EM maps lacking A-site ligands, such as the SecM-stalled ribosome nascent chain complex (26) (Fig. 3D).”
From Structural basis for TetM-mediated tetracycline resistance (2012) · cites this paper as [26]
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- Authors
- Bhushan, S., Hoffmann, T., Seidelt, B., Frauenfeld, J., Mielke, T., Berninghausen, O., Wilson, D. N., & Beckmann, R.
- Affiliations
- Ludwig-Maximilians-Universität München (DE)
- Max Planck Society (DE)
- Center for Integrated Protein Science Munich (DE)
- Corresponding author
- Wilson, Daniel N.
- Beckmann, Roland
- Venue
- PLoS Biology
- Publisher
- Public Library of Science (PLoS)
- Published
- 2011-01-18
- Volume
- 9
- Issue
- 1
- Pages
- e1000581
- ISSN
- 1544-9173 (ISSN-L)
- 1545-7885
- PMC
- PMC3022528
- OpenAlex
- W2168458051
- Cited by
- 154
- References
- 57
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 9 · 2023: 8 · 2022: 5 · 2021: 6 · 2020: 7 · 2019: 6 · 2018: 10 · 2017: 12 · 2016: 12 · 2015: 14 · 2014: 16 · 2013: 13 · 2012: 15
- FWCI
- 7.39
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS Biology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Open access LMU (Ludwid Maxmilian's Universitat Munchen) (submittedVersion)
- Figshare (submittedVersion, cc-by)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Funders
- European Commission
- Deutsche Forschungsgemeinschaft (SFB 646, WI3285/1-1, SFB740, SFB 594)
- 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 › Molecular Biology › RNA modifications and cancer
- Keywords
- SecM, ribosome stalling, peptidyl transferase center, ribosomal tunnel, nascent polypeptide chains, ribosome-nascent chain complex, allosteric regulation, protein secretion, SecA, Escherichia coli
- MeSH terms
- Escherichia coli, Molecular Conformation, Peptidyl Transferases, Ribosomes, RNA, Transfer, Transcription Factors, Protein Biosynthesis, Protein Structure, Tertiary, Catalytic Domain, Cryoelectron Microscopy, Protein Structure, Quaternary, Escherichia coli Proteins
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