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Structural basis for the tryptophan sensitivity of TnaC-mediated ribosome stalling

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  • Anne-Xander Stel

    (Univ. Bordeaux, Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, ARNA, UMR 5320, U1212, Institut Européen de Chimie et Biologie)

  • Emily R. Gordon

    (University of Alabama in Huntsville)

  • Arnab Sengupta

    (University of Alabama in Huntsville)

  • Allyson K. Martínez

    (Texas A&M University)

  • Dorota Klepacki

    (University of Illinois at Chicago)

  • Thomas N. Perry

    (Univ. Bordeaux, Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, ARNA, UMR 5320, U1212, Institut Européen de Chimie et Biologie)

  • Alba Herrero del Valle

    (Univ. Bordeaux, Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, ARNA, UMR 5320, U1212, Institut Européen de Chimie et Biologie)

  • Nora Vázquez-Laslop

    (University of Illinois at Chicago)

  • Matthew S. Sachs

    (Texas A&M University)

  • Luis R. Cruz-Vera

    (University of Alabama in Huntsville)

  • C. Axel Innis

    (Univ. Bordeaux, Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, ARNA, UMR 5320, U1212, Institut Européen de Chimie et Biologie)

Abstract

Free L-tryptophan (L-Trp) stalls ribosomes engaged in the synthesis of TnaC, a leader peptide controlling the expression of the Escherichia coli tryptophanase operon. Despite extensive characterization, the molecular mechanism underlying the recognition and response to L-Trp by the TnaC-ribosome complex remains unknown. Here, we use a combined biochemical and structural approach to characterize a TnaC variant (R23F) with greatly enhanced sensitivity for L-Trp. We show that the TnaC–ribosome complex captures a single L-Trp molecule to undergo termination arrest and that nascent TnaC prevents the catalytic GGQ loop of release factor 2 from adopting an active conformation at the peptidyl transferase center. Importantly, the L-Trp binding site is not altered by the R23F mutation, suggesting that the relative rates of L-Trp binding and peptidyl-tRNA cleavage determine the tryptophan sensitivity of each variant. Thus, our study reveals a strategy whereby a nascent peptide assists the ribosome in detecting a small metabolite.

Suggested Citation

  • Anne-Xander Stel & Emily R. Gordon & Arnab Sengupta & Allyson K. Martínez & Dorota Klepacki & Thomas N. Perry & Alba Herrero del Valle & Nora Vázquez-Laslop & Matthew S. Sachs & Luis R. Cruz-Vera & C., 2021. "Structural basis for the tryptophan sensitivity of TnaC-mediated ribosome stalling," Nature Communications, Nature, vol. 12(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-25663-8
    DOI: 10.1038/s41467-021-25663-8
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    Cited by:

    1. Corentin R. Fostier & Farès Ousalem & Elodie C. Leroy & Saravuth Ngo & Heddy Soufari & C. Axel Innis & Yaser Hashem & Grégory Boël, 2023. "Regulation of the macrolide resistance ABC-F translation factor MsrD," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    2. Felix Gersteuer & Martino Morici & Sara Gabrielli & Keigo Fujiwara & Haaris A. Safdari & Helge Paternoga & Lars V. Bock & Shinobu Chiba & Daniel N. Wilson, 2024. "The SecM arrest peptide traps a pre-peptide bond formation state of the ribosome," Nature Communications, Nature, vol. 15(1), pages 1-16, December.

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