Structural basis for the tryptophan sensitivity of TnaC-mediated ribosome stalling. Academic Article uri icon


  • AbstractFree 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.

published proceedings

  • Nat Commun

altmetric score

  • 17.55

author list (cited authors)

  • van der Stel, A., Gordon, E. R., Sengupta, A., Martínez, A. K., Klepacki, D., Perry, T. N., ... Innis, C. A.

citation count

  • 7

complete list of authors

  • van der Stel, Anne-Xander||Gordon, Emily R||Sengupta, Arnab||Martínez, Allyson K||Klepacki, Dorota||Perry, Thomas N||Herrero Del Valle, Alba||Vázquez-Laslop, Nora||Sachs, Matthew S||Cruz-Vera, Luis R||Innis, C Axel

publication date

  • September 2021