Selection of tRNA by the Ribosome Requires a Transition from an Open to a Closed Form

• Published in: Cell 2002-11, Vol.111 (5), p.721-732
• Main Authors: Ogle, James M., Murphy, Frank V., Tarry, Michael J., Ramakrishnan, V.
• Format: Article
• Language: English
• Subjects: 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; Ribosomes - chemistry; Ribosomes - metabolism; 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; Structure-Activity Relationship; Thermodynamics; Thermus thermophilus
• ISSN: 0092-8674; 1097-4172
• DOI: 10.1016/S0092-8674(02)01086-3

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.