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

<div class='caption-title'>Biochemical characterization of a TnaC(R23F) variant.</div>
<div class='caption-title'>Cryo-EM structure of a TnaC(R23F)–70S complex.</div>
<div class='caption-title'>Contacts between TnaC(R23F) and the ribosome.</div>
van der Stel AX, Gordon ER, Sengupta A, Martínez AK, Klepacki D, Perry TN, Herrero Del Valle A, Vázquez-Laslop N, Sachs MS, Cruz-Vera LR, Innis CA
OpenAccess logo Nat Commun 12 5340 (2021)
Related entries: 7o1a, 7o1c

Cited: 15 times
EuropePMC logo PMID: 34504068

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.

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Reviews citing this publication (5)

  1. Is Protein Folding a Thermodynamically Unfavorable, Active, Energy-Dependent Process? Sorokina I, Mushegian AR, Koonin EV. Int J Mol Sci 23 521 (2022)
  2. Bacterial Ribosome Rescue Systems. Kurita D, Himeno H. Microorganisms 10 372 (2022)
  3. Application of Metabolite-Responsive Biosensors for Plant Natural Products Biosynthesis. Zhang J, Gong X, Gan Q, Yan Y. Biosensors (Basel) 13 633 (2023)
  4. Control of mRNA fate by its encoded nascent polypeptide. Höpfler M, Hegde RS. Mol Cell 83 2840-2855 (2023)
  5. A comprehensive review and comparison of L-tryptophan biosynthesis in Saccharomyces cerevisiae and Escherichia coli. Ren X, Wei Y, Zhao H, Shao J, Zeng F, Wang Z, Li L. Front Bioeng Biotechnol 11 1261832 (2023)

Articles citing this publication (9)

  1. The SecM arrest peptide traps a pre-peptide bond formation state of the ribosome. Gersteuer F, Morici M, Gabrielli S, Fujiwara K, Safdari HA, Paternoga H, Bock LV, Chiba S, Wilson DN. Nat Commun 15 2431 (2024)
  2. Folding of VemP into translation-arresting secondary structure is driven by the ribosome exit tunnel. Kolář MH, Nagy G, Kunkel J, Vaiana SM, Bock LV, Grubmüller H. Nucleic Acids Res 50 2258-2269 (2022)
  3. Regulation of the macrolide resistance ABC-F translation factor MsrD. Fostier CR, Ousalem F, Leroy EC, Ngo S, Soufari H, Innis CA, Hashem Y, Boël G. Nat Commun 14 3891 (2023)
  4. The landscape of translational stall sites in bacteria revealed by monosome and disome profiling. Fujita T, Yokoyama T, Shirouzu M, Taguchi H, Ito T, Iwasaki S. RNA 28 290-302 (2022)
  5. Functional domains of a ribosome arresting peptide are affected by surrounding nonconserved residues. Judd HNG, Martínez AK, Klepacki D, Vázquez-Laslop N, Sachs MS, Cruz-Vera LR. J Biol Chem 300 105780 (2024)
  6. Ribosome Tunnel Environment Drives the Formation of α-Helix during Cotranslational Folding. Yasuda T, Morita R, Shigeta Y, Harada R. J Chem Inf Model 64 6610-6622 (2024)
  7. BEMM-GEN: A Toolkit for Generating a Biomolecular Environment-Mimicking Model for Molecular Dynamics Simulation. Yasuda T, Morita R, Shigeta Y, Harada R. J Chem Inf Model 64 7184-7188 (2024)
  8. Binding of the peptide deformylase on the ribosome surface modulates the exit tunnel interior. McGrath H, Černeková M, Kolář MH. Biophys J 121 4443-4451 (2022)
  9. The Identity of the Constriction Region of the Ribosomal Exit Tunnel Is Important to Maintain Gene Expression in Escherichia coli. Worthan SB, Franklin EA, Pham C, Yap MF, Cruz-Vera LR. Microbiol Spectr 10 e0226121 (2022)


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