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

Author:

van der Stel Anne-Xander,Gordon Emily R.ORCID,Sengupta ArnabORCID,Martínez Allyson K.,Klepacki Dorota,Perry Thomas N.,Herrero del Valle AlbaORCID,Vázquez-Laslop NoraORCID,Sachs Matthew S.ORCID,Cruz-Vera Luis R.ORCID,Innis C. AxelORCID

Abstract

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.

Publisher

Springer Science and Business Media LLC

Subject

General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry

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