title: Structural insights into the translational infidelity mechanism.
abstract: The decoding of mRNA on the ribosome is the least accurate process during genetic information transfer. Here we propose a unified decoding mechanism based on 11 high-resolution X-ray structures of the 70S ribosome that explains the occurrence of missense errors during translation. We determined ribosome structures in rare states where incorrect tRNAs were incorporated into the peptidyl-tRNA-binding site. These structures show that in the codon-anticodon duplex, a G·U mismatch adopts the Watson-Crick geometry, indicating a shift in the tautomeric equilibrium or ionization of the nucleobase. Additional structures with mismatches in the 70S decoding centre show that the binding of any tRNA induces identical rearrangements in the centre, which favours either isosteric or close to the Watson-Crick geometry codon-anticodon pairs. Overall, the results suggest that a mismatch escapes discrimination by preserving the shape of a Watson-Crick pair and indicate that geometric selection via tautomerism or ionization dominates the translational infidelity mechanism.
authors.affiliation: Biologie Structurale Intégrative, Institut de Génétique et de Biologie Moléculaire et Cellulaire, Université de Strasbourg; CNRS, UMR7104; INSERM, U964, Illkirch 67400, France.
authors.forename: Alexey
authors.initials: A
authors.lastname: Rozov
authors.affiliation: Biologie Structurale Intégrative, Institut de Génétique et de Biologie Moléculaire et Cellulaire, Université de Strasbourg; CNRS, UMR7104; INSERM, U964, Illkirch 67400, France.
authors.forename: Natalia
authors.initials: N
authors.lastname: Demeshkina
authors.affiliation: Architecture et Réactivité de l'ARN, Université de Strasbourg, Institut de Biologie Moléculaire et Cellulaire, CNRS, UPR9002, Strasbourg 67084, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Westhof
authors.affiliation: Biologie Structurale Intégrative, Institut de Génétique et de Biologie Moléculaire et Cellulaire, Université de Strasbourg; CNRS, UMR7104; INSERM, U964, Illkirch 67400, France.
authors.forename: Marat
authors.initials: M
authors.lastname: Yusupov
authors.affiliation: Biologie Structurale Intégrative, Institut de Génétique et de Biologie Moléculaire et Cellulaire, Université de Strasbourg; CNRS, UMR7104; INSERM, U964, Illkirch 67400, France.
authors.forename: Gulnara
authors.initials: G
authors.lastname: Yusupova
mesh_terms: D000926:Anticodon / Q000737:chemistry; D020137:Base Pair Mismatch; D020029:Base Pairing; D003062:Codon / Q000737:chemistry; D018360:Crystallography, X-Ray; D014176:Protein Biosynthesis; D012343:RNA, Transfer / Q000737:chemistry / Q000378:metabolism; D012346:RNA, Transfer, Amino Acyl / Q000737:chemistry* / Q000378:metabolism; D012270:Ribosomes / Q000737:chemistry* / Q000378:metabolism; D016963:Thermus thermophilus
chemical_list: D000926:Anticodon; D003062:Codon; D012346:RNA, Transfer, Amino Acyl; C019037:tRNA, peptidyl-; D012343:RNA, Transfer