Selection of tRNA by the ribosome requires a transition from an open to a closed form

Cell. 2002 Nov 27;111(5):721-32. doi: 10.1016/s0092-8674(02)01086-3.

Abstract

A structural and mechanistic explanation for the selection of tRNAs by the ribosome has been elusive. Here, we report crystal structures of the 30S ribosomal subunit with codon and near-cognate tRNA anticodon stem loops bound at the decoding center and compare affinities of equivalent complexes in solution. In ribosomal interactions with near-cognate tRNA, deviation from Watson-Crick geometry results in uncompensated desolvation of hydrogen-bonding partners at the codon-anticodon minor groove. As a result, the transition to a closed form of the 30S induced by cognate tRNA is unfavorable for near-cognate tRNA unless paromomycin induces part of the rearrangement. We conclude that stabilization of a closed 30S conformation is required for tRNA selection, and thereby structurally rationalize much previous data on translational fidelity.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Anti-Bacterial Agents / metabolism
  • Anti-Bacterial Agents / pharmacology
  • Anticodon / chemistry
  • Anticodon / metabolism
  • Base Pairing
  • Binding, Competitive
  • Codon / chemistry
  • Codon / metabolism
  • Crystallography, X-Ray
  • Hydrogen Bonding
  • Models, Molecular
  • Nucleic Acid Conformation
  • Paromomycin / metabolism
  • Paromomycin / pharmacology
  • RNA, Bacterial / chemistry
  • RNA, Bacterial / metabolism
  • RNA, Ribosomal, 16S / chemistry
  • RNA, Ribosomal, 16S / metabolism
  • RNA, Transfer / chemistry*
  • RNA, Transfer / metabolism*
  • RNA, Transfer, Phe / chemistry
  • RNA, Transfer, Phe / metabolism
  • Ribosomes / chemistry
  • Ribosomes / metabolism*
  • Structure-Activity Relationship
  • Thermodynamics
  • Thermus thermophilus

Substances

  • Anti-Bacterial Agents
  • Anticodon
  • Codon
  • RNA, Bacterial
  • RNA, Ribosomal, 16S
  • RNA, Transfer, Phe
  • Paromomycin
  • RNA, Transfer

Associated data

  • PDB/1N32
  • PDB/1N33
  • PDB/1N34
  • PDB/1N36