title: Ribosome Structure Reveals Preservation of Active Sites in the Presence of a P-Site Wobble Mismatch.
abstract: 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.
authors.affiliation: RNA Therapeutics Institute, Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, 368 Plantation Street, Worcester, MA 01605, USA.
authors.forename: Egor
authors.initials: E
authors.lastname: Svidritskiy
authors.affiliation: RNA Therapeutics Institute, Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, 368 Plantation Street, Worcester, MA 01605, USA. Electronic address: andrei.korostelev@umassmed.edu.
authors.forename: Andrei A
authors.initials: AA
authors.lastname: Korostelev
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism; D020029:Base Pairing; D001483:Base Sequence; D020134:Catalytic Domain; D018387:Codon, Initiator / Q000737:chemistry*; D008969:Molecular Sequence Data; D010442:Peptide Chain Initiation, Translational; D011485:Protein Binding; D012333:RNA, Messenger / Q000737:chemistry / Q000378:metabolism; D012343:RNA, Transfer / Q000737:chemistry / Q000378:metabolism; D012270:Ribosomes / Q000737:chemistry* / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D018387:Codon, Initiator; D012333:RNA, Messenger; D012343:RNA, Transfer