title: The ribosome prohibits the G•U wobble geometry at the first position of the codon-anticodon helix.
abstract: Precise conversion of genetic information into proteins is essential to cellular health. However, a margin of error exists and is at its highest on the stage of translation of mRNA by the ribosome. Here we present three crystal structures of 70S ribosome complexes with messenger RNA and transfer RNAs and show that when a G•U base pair is at the first position of the codon-anticodon helix a conventional wobble pair cannot form because of inescapable steric clash between the guanosine of the A codon and the key nucleotide of decoding center adenosine 1493 of 16S rRNA. In our structure the rigid ribosomal decoding center, which is identically shaped for cognate or near-cognate tRNAs, forces this pair to adopt a geometry close to that of a canonical G•C pair. We further strengthen our hypothesis that spatial mimicry due either to base tautomerism or ionization dominates the translation infidelity mechanism.
authors.affiliation: Department of Integrated Structural Biology, Institute of Genetics and Molecular and Cellular Biology, INSERM, U964; CNRS, UMR7104/University of Strasbourg, 1 rue Laurent Fries, 67404 Illkirch, France.
authors.forename: Alexey
authors.initials: A
authors.lastname: Rozov
authors.affiliation: Architecture & Reactivity of RNA, University of Strasbourg, Institute of Molecular and Cellular Biology of the CNRS, UPR9002, 15 rue R. Descartes, 67084 Strasbourg, France.
authors.forename: Eric
authors.identifier: 0000-0002-6172-5422
authors.initials: E
authors.lastname: Westhof
authors.affiliation: Department of Integrated Structural Biology, Institute of Genetics and Molecular and Cellular Biology, INSERM, U964; CNRS, UMR7104/University of Strasbourg, 1 rue Laurent Fries, 67404 Illkirch, France.
authors.forename: Marat
authors.identifier: 0000-0002-9119-9136
authors.initials: M
authors.lastname: Yusupov
authors.affiliation: Department of Integrated Structural Biology, Institute of Genetics and Molecular and Cellular Biology, INSERM, U964; CNRS, UMR7104/University of Strasbourg, 1 rue Laurent Fries, 67404 Illkirch, France gula@igbmc.fr.
authors.forename: Gulnara
authors.identifier: 0000-0002-9119-9136
authors.initials: G
authors.lastname: Yusupova
mesh_terms: D000926:Anticodon / Q000737:chemistry / Q000235:genetics; D003062:Codon / Q000737:chemistry / Q000235:genetics; D018360:Crystallography, X-Ray; D006151:Guanosine / Q000737:chemistry; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000737:chemistry*; D012336:RNA, Ribosomal, 16S / Q000737:chemistry / Q000235:genetics*; D012343:RNA, Transfer / Q000737:chemistry; D012270:Ribosomes / Q000737:chemistry* / Q000235:genetics; D016963:Thermus thermophilus / Q000737:chemistry / Q000235:genetics
chemical_list: D000926:Anticodon; D003062:Codon; D012333:RNA, Messenger; D012336:RNA, Ribosomal, 16S; D006151:Guanosine; D012343:RNA, Transfer