Structural basis for reduced ribosomal A-site fidelity in response to P-site codon-anticodon mismatches

Abstract

Rapid and accurate translation is essential in all organisms to produce properly folded and functional proteins. mRNA codons that define the protein coding sequences are decoded by tRNAs on the ribosome in the aminoacyl (A) binding site. The mRNA codon and the tRNA anticodon interaction is extensively monitored by the ribosome to ensure accuracy in tRNA selection. While other polymerases that synthesize DNA and RNA can correct for misincorporations, the ribosome is unable to correct mistakes. Instead, when a misincorporation occurs, the mismatched tRNA-mRNA pair moves to the peptidyl (P) site and from this location, causes a reduction in the fidelity at the A site, triggering post-peptidyl transfer quality control.