title: A uniform response to mismatches in codon-anticodon complexes ensures ribosomal fidelity.
abstract: Ribosomes take an active part in aminoacyl-tRNA selection by distinguishing correct and incorrect codon-anticodon pairs. Correct codon-anticodon complexes are recognized by a network of ribosome contacts that are specific for each position of the codon-anticodon duplex and involve A-minor RNA interactions. Here, we show by kinetic analysis that single mismatches at any position of the codon-anticodon complex result in slower forward reactions and a uniformly 1000-fold faster dissociation of the tRNA from the ribosome. This suggests that high-fidelity tRNA selection is achieved by a conformational switch of the decoding site between accepting and rejecting modes, regardless of the thermodynamic stability of the respective codon-anticodon complexes or their docking partners at the decoding site. The forward reactions on mismatched codons were particularly sensitive to the disruption of the A-minor interactions with 16S rRNA and determined the variations in the misreading efficiency of near-cognate codons.
authors.affiliation: Institute of Physical Biochemistry, University of Witten/Herdecke, 58448 Witten, Germany.
authors.forename: Kirill B
authors.initials: KB
authors.lastname: Gromadski
authors.forename: Tina
authors.initials: T
authors.lastname: Daviter
authors.forename: Marina V
authors.initials: MV
authors.lastname: Rodnina
mesh_terms: D000818:Animals; D000926:Anticodon; D020137:Base Pair Mismatch; D003062:Codon; D004789:Enzyme Activation; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism; D020558:GTP Phosphohydrolases / Q000378:metabolism; D046911:Macromolecular Substances; D009690:Nucleic Acid Conformation; D010444:Peptide Elongation Factor Tu / Q000378:metabolism; D014176:Protein Biosynthesis; D012345:RNA, Transfer, Amino Acid-Specific / Q000378:metabolism; D012270:Ribosomes / Q000378:metabolism*; D013816:Thermodynamics
chemical_list: D000926:Anticodon; D003062:Codon; D029968:Escherichia coli Proteins; D046911:Macromolecular Substances; D012345:RNA, Transfer, Amino Acid-Specific; D020558:GTP Phosphohydrolases; D010444:Peptide Elongation Factor Tu