Recognition of Cognate Transfer RNA by the 30 <i>S</i> Ribosomal Subunit

TLDR

The ribosomal decoding bases A1492, A1493, and G530 sense Watson‑Crick pairing at the first two codon–anticodon positions and discriminate against near‑cognate tRNAs, while the wobble position tolerates certain noncanonical pairs. High‑resolution crystal structures of the 30 S subunit with mRNA and cognate tRNA, with and without paromomycin, reveal that tRNA binding induces global domain movements and conformational changes of A1492, A1493, and G530, and that paromomycin partially mimics these changes to promote near‑cognate tRNA binding.

Abstract

Crystal structures of the 30 S ribosomal subunit in complex with messenger RNA and cognate transfer RNA in the A site, both in the presence and absence of the antibiotic paromomycin, have been solved at between 3.1 and 3.3 angstroms resolution. Cognate transfer RNA (tRNA) binding induces global domain movements of the 30 S subunit and changes in the conformation of the universally conserved and essential bases A1492, A1493, and G530 of 16 S RNA. These bases interact intimately with the minor groove of the first two base pairs between the codon and anticodon, thus sensing Watson-Crick base-pairing geometry and discriminating against near-cognate tRNA. The third, or “wobble,” position of the codon is free to accommodate certain noncanonical base pairs. By partially inducing these structural changes, paromomycin facilitates binding of near-cognate tRNAs.