7o19

Publication Abstract from PubMed

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.

Structural basis for the tryptophan sensitivity of TnaC-mediated ribosome stalling.,van der Stel AX, Gordon ER, Sengupta A, Martinez AK, Klepacki D, Perry TN, Herrero Del Valle A, Vazquez-Laslop N, Sachs MS, Cruz-Vera LR, Innis CA Nat Commun. 2021 Sep 9;12(1):5340. doi: 10.1038/s41467-021-25663-8. PMID:34504068^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.