Molecular basis for the ribosome functioning as an L-tryptophan sensor

Cell Rep. 2014 Oct 23;9(2):469-75. doi: 10.1016/j.celrep.2014.09.011. Epub 2014 Oct 9.


Elevated levels of the free amino acid L-tryptophan (L-Trp) trigger expression of the tryptophanase tnaCAB operon in E. coli. Activation depends on tryptophan-dependent ribosomal stalling during translation of the upstream TnaC peptide. Here, we present a cryoelectron microscopy (cryo-EM) reconstruction at 3.8 Å resolution of a ribosome stalled by the TnaC peptide. Unexpectedly, we observe two L-Trp molecules in the ribosomal exit tunnel coordinated within composite hydrophobic pockets formed by the nascent TnaC peptide and the tunnel wall. As a result, the peptidyl transferase center (PTC) adopts a distinct conformation that precludes productive accommodation of release factor 2 (RF2), thereby inducing translational stalling. Collectively, our results demonstrate how the translating ribosome can act as a small molecule sensor for gene regulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Escherichia coli / chemistry
  • Escherichia coli / genetics
  • Escherichia coli / metabolism*
  • Escherichia coli Proteins / chemistry
  • Escherichia coli Proteins / metabolism
  • Gene Expression Regulation, Bacterial*
  • Molecular Sequence Data
  • Operon
  • Peptide Termination Factors / metabolism
  • Protein Binding
  • Protein Structure, Tertiary
  • Ribosomes / chemistry*
  • Ribosomes / metabolism
  • Tryptophan / metabolism*


  • Escherichia coli Proteins
  • Peptide Termination Factors
  • peptide chain termination release factor 2
  • tnaC protein, E coli
  • Tryptophan