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Structural insights into the translational infidelity mechanism

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 ribo...

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Autores principales: Rozov, Alexey, Demeshkina, Natalia, Westhof, Eric, Yusupov, Marat, Yusupova, Gulnara
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Pub. Group 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4468848/
https://www.ncbi.nlm.nih.gov/pubmed/26037619
http://dx.doi.org/10.1038/ncomms8251
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author Rozov, Alexey
Demeshkina, Natalia
Westhof, Eric
Yusupov, Marat
Yusupova, Gulnara
author_facet Rozov, Alexey
Demeshkina, Natalia
Westhof, Eric
Yusupov, Marat
Yusupova, Gulnara
author_sort Rozov, Alexey
collection PubMed
description 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.
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spelling pubmed-44688482015-06-30 Structural insights into the translational infidelity mechanism Rozov, Alexey Demeshkina, Natalia Westhof, Eric Yusupov, Marat Yusupova, Gulnara Nat Commun Article 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. Nature Pub. Group 2015-06-03 /pmc/articles/PMC4468848/ /pubmed/26037619 http://dx.doi.org/10.1038/ncomms8251 Text en Copyright © 2015, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Rozov, Alexey
Demeshkina, Natalia
Westhof, Eric
Yusupov, Marat
Yusupova, Gulnara
Structural insights into the translational infidelity mechanism
title Structural insights into the translational infidelity mechanism
title_full Structural insights into the translational infidelity mechanism
title_fullStr Structural insights into the translational infidelity mechanism
title_full_unstemmed Structural insights into the translational infidelity mechanism
title_short Structural insights into the translational infidelity mechanism
title_sort structural insights into the translational infidelity mechanism
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4468848/
https://www.ncbi.nlm.nih.gov/pubmed/26037619
http://dx.doi.org/10.1038/ncomms8251
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