Ribosome Structure Reveals Preservation of Active Sites in the Presence of a P-Site Wobble Mismatch
RNA Therapeutics Institute; Department of Biochemistry and Molecular Pharmacology
Biochemistry, Biophysics, and Structural Biology | Cell and Developmental Biology | Genetics and Genomics | Therapeutics
Translation initiation in the P site occasionally occurs at atypical (non-AUG) start codons, including those forming a mismatch in the third (wobble) position. During elongation, however, a pyrimidine-pyrimidine wobble mismatch may trigger a translation quality-control mechanism, whereby the P-site mismatch is thought to perturb the downstream A-site codon or the decoding center, thereby reducing translation fidelity and inducing termination of aberrant translation. We report a crystal structure of the 70S initiation complex containing an AUC codon in the ribosomal P site. Remarkably, the ribosome stabilizes the mismatched codon-anticodon helix, arranging a normally disruptive cytosine-cytosine pair into a Watson-Crick-like conformation. Translation-competent conformations of the tRNA, mRNA, and decoding center suggest that a P-site wobble-position mismatch in the 70S initiation complex does not pre-arrange the mRNA or decoding center to favor subsequent miscoding events.
DOI of Published Version
Structure. 2015 Nov 3;23(11):2155-61. doi: 10.1016/j.str.2015.08.011. Epub 2015 Sep 24. Link to article on publisher's site
Structure (London, England : 1993)
Svidritskiy, Egor and Korostelev, Andrei A., "Ribosome Structure Reveals Preservation of Active Sites in the Presence of a P-Site Wobble Mismatch" (2015). RNA Therapeutics Institute Publications. 22.