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RAPP-containing arrest peptides induce translational stalling by short circuiting the ribosomal peptidyltransferase activity

Author

Listed:
  • Martino Morici

    (University of Hamburg)

  • Sara Gabrielli

    (Max Planck Institute for Multidisciplinary Sciences)

  • Keigo Fujiwara

    (Kyoto Sangyo University)

  • Helge Paternoga

    (University of Hamburg)

  • Bertrand Beckert

    (University of Hamburg)

  • Lars V. Bock

    (Max Planck Institute for Multidisciplinary Sciences)

  • Shinobu Chiba

    (Kyoto Sangyo University)

  • Daniel N. Wilson

    (University of Hamburg)

Abstract

Arrest peptides containing RAPP (ArgAlaProPro) motifs have been discovered in both Gram-positive and Gram-negative bacteria, where they are thought to regulate expression of important protein localization machinery components. Here we determine cryo-EM structures of ribosomes stalled on RAPP arrest motifs in both Bacillus subtilis and Escherichia coli. Together with molecular dynamics simulations, our structures reveal that the RAPP motifs allow full accommodation of the A-site tRNA, but prevent the subsequent peptide bond from forming. Our data support a model where the RAP in the P-site interacts and stabilizes a single hydrogen atom on the Pro-tRNA in the A-site, thereby preventing an optimal geometry for the nucleophilic attack required for peptide bond formation to occur. This mechanism to short circuit the ribosomal peptidyltransferase activity is likely to operate for the majority of other RAPP-like arrest peptides found across diverse bacterial phylogenies.

Suggested Citation

  • Martino Morici & Sara Gabrielli & Keigo Fujiwara & Helge Paternoga & Bertrand Beckert & Lars V. Bock & Shinobu Chiba & Daniel N. Wilson, 2024. "RAPP-containing arrest peptides induce translational stalling by short circuiting the ribosomal peptidyltransferase activity," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-46761-3
    DOI: 10.1038/s41467-024-46761-3
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    References listed on IDEAS

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    1. Stefan Arenz & Lars V. Bock & Michael Graf & C. Axel Innis & Roland Beckmann & Helmut Grubmüller & Andrea C. Vaiana & Daniel N. Wilson, 2016. "A combined cryo-EM and molecular dynamics approach reveals the mechanism of ErmBL-mediated translation arrest," Nature Communications, Nature, vol. 7(1), pages 1-14, November.
    2. T. Martin Schmeing & Kevin S. Huang & Scott A. Strobel & Thomas A. Steitz, 2005. "An induced-fit mechanism to promote peptide bond formation and exclude hydrolysis of peptidyl-tRNA," Nature, Nature, vol. 438(7067), pages 520-524, November.
    3. Daniel Sohmen & Shinobu Chiba & Naomi Shimokawa-Chiba & C. Axel Innis & Otto Berninghausen & Roland Beckmann & Koreaki Ito & Daniel N. Wilson, 2015. "Structure of the Bacillus subtilis 70S ribosome reveals the basis for species-specific stalling," Nature Communications, Nature, vol. 6(1), pages 1-10, November.
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    Cited by:

    1. Keigo Fujiwara & Naoko Tsuji & Mayu Yoshida & Hiraku Takada & Shinobu Chiba, 2024. "Patchy and widespread distribution of bacterial translation arrest peptides associated with the protein localization machinery," Nature Communications, Nature, vol. 15(1), pages 1-16, December.

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