Structural insight into nascent polypeptide chain-mediated translational stalling

Science. 2009 Dec 4;326(5958):1412-5. doi: 10.1126/science.1177662. Epub 2009 Oct 29.


Expression of the Escherichia coli tryptophanase operon depends on ribosome stalling during translation of the upstream TnaC leader peptide, a process for which interactions between the TnaC nascent chain and the ribosomal exit tunnel are critical. We determined a 5.8 angstrom-resolution cryo-electron microscopy and single-particle reconstruction of a ribosome stalled during translation of the tnaC leader gene. The nascent chain was extended within the exit tunnel, making contacts with ribosomal components at distinct sites. Upon stalling, two conserved residues within the peptidyltransferase center adopted conformations that preclude binding of release factors. We propose a model whereby interactions within the tunnel are relayed to the peptidyltransferase center to inhibit translation. Moreover, we show that nascent chains adopt distinct conformations within the ribosomal exit tunnel.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Binding Sites
  • Cryoelectron Microscopy
  • Escherichia coli / genetics*
  • Escherichia coli / metabolism
  • Escherichia coli Proteins / chemistry*
  • Escherichia coli Proteins / genetics
  • Escherichia coli Proteins / metabolism*
  • Escherichia coli Proteins / ultrastructure
  • Gene Expression Regulation, Bacterial
  • Image Processing, Computer-Assisted
  • Models, Biological
  • Models, Molecular
  • Operon
  • Peptidyl Transferases / metabolism
  • Protein Biosynthesis*
  • Protein Conformation
  • RNA-Binding Proteins / chemistry
  • RNA-Binding Proteins / metabolism
  • RNA-Binding Proteins / ultrastructure
  • Ribosomal Proteins / chemistry
  • Ribosomal Proteins / metabolism
  • Ribosomal Proteins / ultrastructure
  • Ribosomes / metabolism*
  • Ribosomes / ultrastructure
  • Tryptophanase / biosynthesis
  • Tryptophanase / genetics*


  • Escherichia coli Proteins
  • RNA-Binding Proteins
  • Ribosomal Proteins
  • rplV protein, E coli
  • tnaC protein, E coli
  • Peptidyl Transferases
  • Tryptophanase

Associated data

  • PDB/2WWL
  • PDB/2WWQ