Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

An antimicrobial peptide that inhibits translation by trapping release factors on the ribosome

Nature Structural & Molecular Biology volume 24, pages 752–757 (2017)Cite this article

Subjects

Abstract

Many antibiotics stop bacterial growth by inhibiting different steps of protein synthesis. However, no specific inhibitors of translation termination are known. Proline-rich antimicrobial peptides, a component of the antibacterial defense system of multicellular organisms, interfere with bacterial growth by inhibiting translation. Here we show that Api137, a derivative of the insect-produced antimicrobial peptide apidaecin, arrests terminating ribosomes using a unique mechanism of action. Api137 binds to the Escherichia coli ribosome and traps release factor (RF) RF1 or RF2 subsequent to the release of the nascent polypeptide chain. A high-resolution cryo-EM structure of the ribosome complexed with RF1 and Api137 reveals the molecular interactions that lead to RF trapping. Api137-mediated depletion of the cellular pool of free release factors causes the majority of ribosomes to stall at stop codons before polypeptide release, thereby resulting in a global shutdown of translation termination.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Api137 stalls ribosomes at the termination step of translation.
Figure 2: Api137 allows peptide hydrolysis but inhibits turnover of RF1 and RF2.
Figure 3: Binding of Api137 to the terminating ribosome and its interactions with the exit tunnel.
Figure 4: Inhibitory action of Api137 is mediated by its interactions with RF1 and P-site tRNA.
Figure 5: Api137 induces accumulation of peptidyl-tRNA and stop codon readthrough.

Similar content being viewed by others

Accession codes

Primary accessions

Electron Microscopy Data Bank

Protein Data Bank

Referenced accessions

Protein Data Bank

References

  1. Korostelev, A.A. Structural aspects of translation termination on the ribosome. RNA 17, 1409–1421 (2011).

    Article  CAS  Google Scholar 

  2. Bremer, H. & Dennis, P. in Escherichia coli and Salmonella: Cellular and Molecular Biology Vol. 2 (eds. Neidhardt, F.C. et al.) Ch. 97 (ASM Press, 1996).

  3. Schmidt, A. et al. The quantitative and condition-dependent Escherichia coli proteome. Nat. Biotechnol. 34, 104–110 (2016).

    Article  CAS  Google Scholar 

  4. Koutmou, K.S., McDonald, M.E., Brunelle, J.L. & Green, R. RF3:GTP promotes rapid dissociation of the class 1 termination factor. RNA 20, 609–620 (2014).

    Article  CAS  Google Scholar 

  5. Shi, X. & Joseph, S. Mechanism of translation termination: RF1 dissociation follows dissociation of RF3 from the ribosome. Biochemistry 55, 6344–6354 (2016).

    Article  CAS  Google Scholar 

  6. Kaji, A. et al. The fourth step of protein synthesis: disassembly of the posttermination complex is catalyzed by elongation factor G and ribosome recycling factor, a near-perfect mimic of tRNA. Cold Spring Harb. Symp. Quant. Biol. 66, 515–530 (2001).

    Article  CAS  Google Scholar 

  7. Zasloff, M. Antimicrobial peptides of multicellular organisms. Nature 415, 389–395 (2002).

    Article  CAS  Google Scholar 

  8. Scocchi, M., Mardirossian, M., Runti, G. & Benincasa, M. Non-membrane permeabilizing modes of action of antimicrobial peptides on bacteria. Curr. Top. Med. Chem. 16, 76–88 (2016).

    Article  CAS  Google Scholar 

  9. Li, W. et al. Proline-rich antimicrobial peptides: potential therapeutics against antibiotic-resistant bacteria. Amino Acids 46, 2287–2294 (2014).

    Article  CAS  Google Scholar 

  10. Seefeldt, A.C. et al. Structure of the mammalian antimicrobial peptide Bac7(1-16) bound within the exit tunnel of a bacterial ribosome. Nucleic Acids Res. 44, 2429–2438 (2016).

    Article  CAS  Google Scholar 

  11. Roy, R.N., Lomakin, I.B., Gagnon, M.G. & Steitz, T.A. The mechanism of inhibition of protein synthesis by the proline-rich peptide oncocin. Nat. Struct. Mol. Biol. 22, 466–469 (2015).

    Article  CAS  Google Scholar 

  12. Seefeldt, A.C. et al. The proline-rich antimicrobial peptide Onc112 inhibits translation by blocking and destabilizing the initiation complex. Nat. Struct. Mol. Biol. 22, 470–475 (2015).

    Article  CAS  Google Scholar 

  13. Gagnon, M.G. et al. Structures of proline-rich peptides bound to the ribosome reveal a common mechanism of protein synthesis inhibition. Nucleic Acids Res. 44, 2439–2450 (2016).

    Article  CAS  Google Scholar 

  14. Krizsan, A., Prahl, C., Goldbach, T., Knappe, D. & Hoffmann, R. Short proline-rich antimicrobial peptides inhibit either the bacterial 70S ribosome or the assembly of its large 50S subunit. ChemBioChem 16, 2304–2308 (2015).

    Article  CAS  Google Scholar 

  15. Castle, M., Nazarian, A., Yi, S.S. & Tempst, P. Lethal effects of apidaecin on Escherichia coli involve sequential molecular interactions with diverse targets. J. Biol. Chem. 274, 32555–32564 (1999).

    Article  CAS  Google Scholar 

  16. Krizsan, A. et al. Insect-derived proline-rich antimicrobial peptides kill bacteria by inhibiting bacterial protein translation at the 70S ribosome. Angew. Chem. Int. Edn Engl. 53, 12236–12239 (2014).

    Article  CAS  Google Scholar 

  17. Berthold, N. et al. Novel apidaecin 1b analogs with superior serum stabilities for treatment of infections by gram-negative pathogens. Antimicrob. Agents Chemother. 57, 402–409 (2013).

    Article  CAS  Google Scholar 

  18. Hartz, D., McPheeters, D.S., Traut, R. & Gold, L. Extension inhibition analysis of translation initiation complexes. Methods Enzymol. 164, 419–425 (1988).

    Article  CAS  Google Scholar 

  19. Mattiuzzo, M. et al. Role of the Escherichia coli SbmA in the antimicrobial activity of proline-rich peptides. Mol. Microbiol. 66, 151–163 (2007).

    Article  CAS  Google Scholar 

  20. Uno, M., Ito, K. & Nakamura, Y. Functional specificity of amino acid at position 246 in the tRNA mimicry domain of bacterial release factor 2. Biochimie 78, 935–943 (1996).

    Article  CAS  Google Scholar 

  21. Dreyfus, M. & Heurgué-Hamard, V. Termination troubles in Escherichia coli K12. Mol. Microbiol. 79, 288–291 (2011).

    Article  CAS  Google Scholar 

  22. Kuhlenkoetter, S., Wintermeyer, W. & Rodnina, M.V. Different substrate-dependent transition states in the active site of the ribosome. Nature 476, 351–354 (2011).

    Article  CAS  Google Scholar 

  23. Korostelev, A., Zhu, J., Asahara, H. & Noller, H.F. Recognition of the amber UAG stop codon by release factor RF1. EMBO J. 29, 2577–2585 (2010).

    Article  CAS  Google Scholar 

  24. Pierson, W.E. et al. Uniformity of peptide release is maintained by methylation of release factors. Cell Rep. 17, 11–18 (2016).

    Article  CAS  Google Scholar 

  25. Gao, H. et al. RF3 induces ribosomal conformational changes responsible for dissociation of class I release factors. Cell 129, 929–941 (2007).

    Article  CAS  Google Scholar 

  26. Gong, F. & Yanofsky, C. Instruction of translating ribosome by nascent peptide. Science 297, 1864–1867 (2002).

    Article  CAS  Google Scholar 

  27. Uehara, Y., Hori, M. & Umezawa, H. Specific inhibition of the termination process of protein synthesis by negamycin. Biochim. Biophys. Acta 442, 251–262 (1976).

    Article  CAS  Google Scholar 

  28. Svidritskiy, E., Ling, C., Ermolenko, D.N. & Korostelev, A.A. Blasticidin S inhibits translation by trapping deformed tRNA on the ribosome. Proc. Natl. Acad. Sci. USA 110, 12283–12288 (2013).

    Article  CAS  Google Scholar 

  29. Des Soye, B.J., Patel, J.R., Isaacs, F.J. & Jewett, M.C. Repurposing the translation apparatus for synthetic biology. Curr. Opin. Chem. Biol. 28, 83–90 (2015).

    Article  CAS  Google Scholar 

  30. Keeling, K.M., Xue, X., Gunn, G. & Bedwell, D.M. Therapeutics based on stop codon readthrough. Annu. Rev. Genomics Hum. Genet. 15, 371–394 (2014).

    Article  CAS  Google Scholar 

  31. Roy, B. et al. Ataluren stimulates ribosomal selection of near-cognate tRNAs to promote nonsense suppression. Proc. Natl. Acad. Sci. USA 113, 12508–12513 (2016).

    Article  CAS  Google Scholar 

  32. Vazquez-Laslop, N., Thum, C. & Mankin, A.S. Molecular mechanism of drug-dependent ribosome stalling. Mol. Cell 30, 190–202 (2008).

    Article  CAS  Google Scholar 

  33. Orelle, C. et al. Identifying the targets of aminoacyl-tRNA synthetase inhibitors by primer extension inhibition. Nucleic Acids Res. 41, e144 (2013).

    Article  CAS  Google Scholar 

  34. Quan, S., Skovgaard, O., McLaughlin, R.E., Buurman, E.T. & Squires, C.L. Markerless Escherichia coli rrn deletion strains for genetic determination of ribosomal binding sites. G3 (Bethesda) 5, 2555–2557 (2015).

    Article  CAS  Google Scholar 

  35. Bailey, M., Chettiath, T. & Mankin, A.S. Induction of erm(C) expression by noninducing antibiotics. Antimicrob. Agents Chemother. 52, 866–874 (2008).

    Article  CAS  Google Scholar 

  36. Rodnina, M.V. & Wintermeyer, W. GTP consumption of elongation factor Tu during translation of heteropolymeric mRNAs. Proc. Natl. Acad. Sci. USA 92, 1945–1949 (1995).

    Article  CAS  Google Scholar 

  37. Milon, P. et al. Transient kinetics, fluorescence, and FRET in studies of initiation of translation in bacteria. Methods Enzymol. 430, 1–30 (2007).

    Article  CAS  Google Scholar 

  38. Peske, F., Kuhlenkoetter, S., Rodnina, M.V. & Wintermeyer, W. Timing of GTP binding and hydrolysis by translation termination factor RF3. Nucleic Acids Res. 42, 1812–1820 (2014).

    Article  CAS  Google Scholar 

  39. Merryman, C. & Noller, H.F. in RNA:Protein Interactions, A Practical Approach (ed. Smith, C.W.J.) 237–253 (Oxford University Press, 1998).

  40. Schägger, H. & von Jagow, G. Tricine-sodium dodecyl sulfate-polyacrylamide gel electrophoresis for the separation of proteins in the range from 1 to 100 kDa. Anal. Biochem. 166, 368–379 (1987).

    Article  Google Scholar 

  41. Arenz, S., Nguyen, F., Beckmann, R. & Wilson, D.N. Cryo-EM structure of the tetracycline resistance protein TetM in complex with a translating ribosome at 3.9-Å resolution. Proc. Natl. Acad. Sci. USA 112, 5401–5406 (2015).

    Article  CAS  Google Scholar 

  42. Arenz, S. et al. Molecular basis for erythromycin-dependent ribosome stalling during translation of the ErmBL leader peptide. Nat. Commun. 5, 3501 (2014).

    Article  Google Scholar 

  43. Li, X. et al. Electron counting and beam-induced motion correction enable near-atomic-resolution single-particle cryo-EM. Nat. Methods 10, 584–590 (2013).

    Article  CAS  Google Scholar 

  44. Rohou, A. & Grigorieff, N. CTFFIND4: fast and accurate defocus estimation from electron micrographs. J. Struct. Biol. 192, 216–221 (2015).

    Article  Google Scholar 

  45. Chen, J.Z. & Grigorieff, N. SIGNATURE: a single-particle selection system for molecular electron microscopy. J. Struct. Biol. 157, 168–173 (2007).

    Article  CAS  Google Scholar 

  46. Grigorieff, N. FREALIGN: high-resolution refinement of single particle structures. J. Struct. Biol. 157, 117–125 (2007).

    Article  CAS  Google Scholar 

  47. Kucukelbir, A., Sigworth, F.J. & Tagare, H.D. Quantifying the local resolution of cryo-EM density maps. Nat. Methods 11, 63–65 (2014).

    Article  CAS  Google Scholar 

  48. Scheres, S.H. RELION: implementation of a Bayesian approach to cryo-EM structure determination. J. Struct. Biol. 180, 519–530 (2012).

    Article  CAS  Google Scholar 

  49. Fischer, N. et al. Structure of the E. coli ribosome-EF-Tu complex at <3 Å resolution by Cs-corrected cryo-EM. Nature 520, 567–570 (2015).

    Article  Google Scholar 

  50. Huter, P. et al. Structural basis for ArfA-RF2-mediated translation termination on mRNAs lacking stop codons. Nature 541, 546–549 (2017).

    Article  CAS  Google Scholar 

  51. Emsley, P. & Cowtan, K. Coot: model-building tools for molecular graphics. Acta Crystallogr. D Biol. Crystallogr. 60, 2126–2132 (2004).

    Article  Google Scholar 

  52. Adams, P.D. et al. PHENIX: a comprehensive Python-based system for macromolecular structure solution. Acta Crystallogr. D Biol. Crystallogr. 66, 213–221 (2010).

    Article  CAS  Google Scholar 

  53. Brown, A. et al. Tools for macromolecular model building and refinement into electron cryo-microscopy reconstructions. Acta Crystallogr. D Biol. Crystallogr. 71, 136–153 (2015).

    Article  CAS  Google Scholar 

  54. Chen, V.B. et al. MolProbity: all-atom structure validation for macromolecular crystallography. Acta Crystallogr. D Biol. Crystallogr. 66, 12–21 (2010).

    Article  CAS  Google Scholar 

  55. Pettersen, E.F. et al. UCSF Chimera—a visualization system for exploratory research and analysis. J. Comput. Chem. 25, 1605–1612 (2004).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank I. Lomakin and M. Gagnon for helping us initiate this project. We also thank them and Y. Polikanov for critical discussions, T. Perez-Morales for experimental advice, A. Kefi for help with analysis of genome sequencing data, A. Bursy, O. Geintzer, S. Kappler, C. Kothe, T. Niese, S. Rieder, H. Sieber, T. Wiles, and M. Zimmermann for expert technical assistance. This work was supported by grant R01 GM 106386 from the US National Institutes of Health (to A.S.M. and N.V.-L.), iNEXT project 2259 (to D.N.W.), grants of the Forschergruppe FOR 1805 (to D.N.W., R.B. and M.V.R.) and a project grant in the framework of the Sonderforschungsbereich SFB860 (to M.V.R.) from the Deutsche Forschungsgemeinschaft (DFG).

Author information

Author notes

  1. Tanja Florin, Cristina Maracci and Michael Graf: These authors contributed equally to this work.

Authors and Affiliations

  1. Center for Biomolecular Sciences, University of Illinois at Chicago, Chicago, Illinois, USA

    Tanja Florin, Dorota Klepacki, Nora Vázquez-Laslop & Alexander S Mankin

  2. Department of Physical Biochemistry, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany

    Cristina Maracci, Prajwal Karki & Marina V Rodnina

  3. Department for Biochemistry and Center for Protein Science Munich (CiPSM), Gene Center, University of Munich, Munich, Germany

    Michael Graf, Otto Berninghausen, Roland Beckmann & Daniel N Wilson

  4. Institute for Biochemistry and Molecular Biology, University of Hamburg, Hamburg, Germany

    Daniel N Wilson

Authors
  1. Tanja Florin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Cristina Maracci
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Michael Graf
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Prajwal Karki
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Dorota Klepacki
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Otto Berninghausen
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Roland Beckmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Nora Vázquez-Laslop
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Daniel N Wilson
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Marina V Rodnina
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Alexander S Mankin
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Members of the A.S.M. and N.V.-L. labs (T.F., D.K., N.V.-L. and A.S.M.) carried out biochemical, microbiological and genetic experiments. Members of the M.V.R. lab (C.M., P.K. and M.V.R.) performed kinetic analysis, and members of the D.N.W. lab (M.G., O.B., R.B. and D.N.W.) carried out structural studies. N.V.-L., A.S.M., M.V.R. and D.N.W. designed the study and oversaw the experiments. T.F., C.M. and M.G. designed and performed the experiments and analyzed the data. P.K. and D.K. performed the experiments. N.V.-L., A.S.M., M.V.R., D.N.W., T.F., C.M. and M.G. wrote the paper.

Corresponding authors

Correspondence to Nora Vázquez-Laslop, Daniel N Wilson, Marina V Rodnina or Alexander S Mankin.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Integrated supplementary information

Supplementary Figure 1 Api137-induced ribosome stalling at the end of the ORFs

Toeprinting analysis of translation arrest in the synthetic ORF RST2 (left) and the natural ORF ermBL (right) mediated by PrAMPs. The toeprint bands corresponding to the ribosomes arrested by Api137 or the natural apidaecin 1a (Api1a) at the stop codon of the ORF are indicated with orange arrowheads; the bands representing the ribosome arrested by Onc112 at the start codon are marked with blue arrowheads. Sequencing lanes are shown. The nucleotides corresponding to the toeprint bands are indicated in the gene sequence on the side of the gels; orange brackets indicate codons positioned in the P- and A- sites of the Api-stalled ribosome; blue brackets indicate codons in the P- and A- sites of the Onc112-stalled ribosome. The gels are representatives of two independent experiments.

Supplementary Figure 2 Api137-resistance mutations.

a, Effect of the newly-isolated (marked by asterisks) or tested mutations on sensitivity of E. coli cells to Api137. The RF1 mutation is highlighted in orange; RF2 mutations, teal; rRNA mutations. gray; uL16, brown; uL4, blue; uL22, purple. Each MIC was determined in at least two independent experiments. b-d, Location of resistance mutations within the context of the terminating ribosome. b, Transverse section of the 50S ribosomal subunit (gray) of the 70S ribosome (30S subunit, yellow) showing the location of ribosomal proteins uL4, uL16, uL22 or 23S rRNA nucleotides (gray) whose mutations confer resistance to Api137. The region enlarged in (c) is boxed. c-d, Location of Api137 resistance mutations (spheres) in 23S rRNA (gray), ribosomal proteins uL4 (blue), uL16 (brown) and uL22 (purple), as well as (c) RF1 (orange) or (d) RF2 (teal). The GGQ motif of RF1 and RF2 is colored red in (c) and (d).

Supplementary Figure 3 Mutations allow faster dissociation of RF1 and RF2 from the PostHC.

a, Dissociation of RF1(D241G) from the PostHC in the presence of Api137. RF1(D241G)Qsy was incubated with PreHCFlu (0.05 μM) to generate PostHCFlu and then mixed with a 10-fold excess of unlabeled RF1 and RF3·GTP in the absence (gray) or in the presence (black) of Api137 (1 μM). The traces represent the average of up to eight technical replicates. No dissociation of wt RF1 in the presence of Api137 was observed under the same experimental conditions (Fig. 2f). b, Peptide hydrolysis by K12 strain-specific RF2(Ala246Thr) at turnover conditions in the absence (open circles) or in the presence (closed circles) of Api137 (1 μM). In the presence of Api137, the peptide hydrolysis reaction proceeds faster when it is catalyzed by the K12 strain RF2, compared to the B strain RF2 (Fig. 2c).

Source data

Supplementary Figure 4 In silico sorting and resolution of the Api-RF1-70S complex.

a, In silico sorting was performed with the FreAlign 9.11 software package (as described in Grigorieff, N., J. Struct. Biol. 157, 117-125 (2007)). Initial alignment of 116,212 particles was followed by 3D classification, resulting in six different classes. Class 1 (38,203 particles) was further refined, yielding a (b) final reconstruction consisting of 36,826 particles, with (c) an average resolution of 3.4 Å (based on the Fourier shell correlation (FSC) curve at FSC 0.143). d, Validation of the fit of molecular models to cryo-EM map for the Api137-RF1-70S complex. FSC curves calculated between the refined model and the final map (blue), with the self- and cross-validated correlations in orange and black, respectively. Information beyond 3.4 Å was not used during refinement and preserved for validation. (e) Side view and (f) transverse section of the cryo-EM map of Api137-RF1-70S complex colored according to local resolution as shown previously (Kucukelbir, A., Sigworth, F. J. & Tagare, H. D., Nat. Methods 11, 63-65 (2014)). g-h, Cryo-EM density for Api137 (g) colored according to local resolution and (h) shown as gray mesh with molecular model for residues 5-18.

Supplementary Figure 5 Features of the Api137-RF1-70S complex.

a, RF1 (orange), deacylated P-site tRNA (green) and Api137 (salmon) in the Api137-RF1-70S complex. The position of RF1 during canonical termination is shown in blue (PDBID 5J30; Pierson, W. E. et al., Cell Rep. 17, 11-18 (2016)). Boxed regions are zoomed in the panels (b) and (c). b, Interaction of the PAT motif of RF1 (orange) with the UAG stop codon of the mRNA (cyan) in the Api137-RF1-70S complex. c, A2602 of the 23S rRNA is in the rotated conformation as observed in previous RF1-70S structures (Korostelev, A. et al., EMBO J. 29, 2577-2585 (2010); Pierson, W. E. et al., Cell Rep. 17, 11-18 (2016); Laurberg, M. et al., Nature 454, 852-857 (2008); Svidritskiy, E. & Korostelev, A. A., Structure 23, 2155-2161 (2015)). Conformation of A2602 (gray) in Api137-RF1-70S complex compared to A2602 (blue) during canonical termination (PDBID 5J30; Pierson, W. E. et al., Cell Rep. 17, 11-18 (2016)) and A2602 (slate) from the pre-attack state (PDBID 1VY4; Polikanov, Y. S., Steitz, T. A. & Innis, C. A., Nat. Struct. Mol. Biol. 21, 787-793 (2014)). Api137 (salmon) and P-site tRNA (green) are shown for reference. d, e, The binding position of Api137 (salmon) relative to the (d) MifM nascent chain (dark green; Sohmen, D. et al., Nat. Commun. 6, 6941 (2015)) or (e) antimicrobial peptide Onc112 (slate; Seefeldt, A. C. et al., Nat. Struct. Mol. Biol. 22, 470-475 (2015)). In (d) and (e) the orientations of the peptides are indicated.

Supplementary Figure 6 Mutations that increase resistance to Api137.

(a-c) Location of residues in (a) RF1 (orange) and (b, c) RF2 (teal) that increase resistance to Api137 when mutated. Site of mutations are shown in stick and surface representation and glutamines of the GGQ motif (Gln235 in RF1 and Gln252 in RF2) are shown as sticks for reference. (d-f) Location of Api137 resistance mutations in ribosomal proteins. (d) Lys63 in uL4 (blue) interacts with 23S rRNA residues G2061 and G2444. (e) Deletion of 82MKR84 (outside of the figure boundaries) in uL22 (purple) confers resistance to Api137 presumably by changing the geometry of the uL22 exit tunnel loop and disrupting Api137 interaction with neighboring 23S rRNA nucleotides (gray), such as A751. (f) The mutation of Arg81 in uL16 (brown) may relieve Api137-mediated RF1 and RF2 trapping by indirectly destabilizing interactions of deacylated tRNA with the P-site mediated by G2251 of the 23S rRNA.

Supplementary information

Supplementary Text and Figures

Supplementary Figures 1–6 and Supplementary Tables 1–4 (PDF 1677 kb)

Life Sciences Reporting Summary (PDF 129 kb)

Source data

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Florin, T., Maracci, C., Graf, M. et al. An antimicrobial peptide that inhibits translation by trapping release factors on the ribosome. Nat Struct Mol Biol 24, 752–757 (2017). https://doi.org/10.1038/nsmb.3439

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nsmb.3439

This article is cited by

Search

Advanced search

Quick links

Nature Briefing Microbiology

Sign up for the Nature Briefing: Microbiology newsletter — what matters in microbiology research, free to your inbox weekly.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing: Microbiology