Why base tautomerization does not cause errors in mRNA decoding on the ribosome
The structure of the genetic code implies strict Watson–Crick base pairing in the first two codon positions, while the third position is known to be degenerate, thus allowing wobble base pairing. Recent crystal structures of near-cognate tRNAs accommodated into the ribosomal A-site, however, show ca...
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| Format: | Online |
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Oxford University Press
2014
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4227757/ |
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pubmed-42277572014-11-21 Why base tautomerization does not cause errors in mRNA decoding on the ribosome Satpati, Priyadarshi Åqvist, Johan RNA The structure of the genetic code implies strict Watson–Crick base pairing in the first two codon positions, while the third position is known to be degenerate, thus allowing wobble base pairing. Recent crystal structures of near-cognate tRNAs accommodated into the ribosomal A-site, however, show canonical geometry even with first and second position mismatches. This immediately raises the question of whether these structures correspond to tautomerization of the base pairs. Further, if unusual tautomers are indeed trapped why do they not cause errors in decoding? Here, we use molecular dynamics free energy calculations of ribosomal complexes with cognate and near-cognate tRNAs to analyze the structures and energetics of G-U mismatches in the first two codon positions. We find that the enol tautomer of G is almost isoenergetic with the corresponding ketone in the first position, while it is actually more stable in the second position. Tautomerization of U, on the other hand is highly penalized. The presence of the unusual enol form of G thus explains the crystallographic observations. However, the calculations also show that this tautomer does not cause high codon reading error frequencies, as the resulting tRNA binding free energies are significantly higher than for the cognate complex. Oxford University Press 2014-11-10 2014-10-28 /pmc/articles/PMC4227757/ /pubmed/25352546 http://dx.doi.org/10.1093/nar/gku1044 Text en © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Satpati, Priyadarshi Åqvist, Johan |
| spellingShingle |
Satpati, Priyadarshi Åqvist, Johan Why base tautomerization does not cause errors in mRNA decoding on the ribosome |
| author_facet |
Satpati, Priyadarshi Åqvist, Johan |
| author_sort |
Satpati, Priyadarshi |
| title |
Why base tautomerization does not cause errors in mRNA decoding on the ribosome |
| title_short |
Why base tautomerization does not cause errors in mRNA decoding on the ribosome |
| title_full |
Why base tautomerization does not cause errors in mRNA decoding on the ribosome |
| title_fullStr |
Why base tautomerization does not cause errors in mRNA decoding on the ribosome |
| title_full_unstemmed |
Why base tautomerization does not cause errors in mRNA decoding on the ribosome |
| title_sort |
why base tautomerization does not cause errors in mrna decoding on the ribosome |
| description |
The structure of the genetic code implies strict Watson–Crick base pairing in the first two codon positions, while the third position is known to be degenerate, thus allowing wobble base pairing. Recent crystal structures of near-cognate tRNAs accommodated into the ribosomal A-site, however, show canonical geometry even with first and second position mismatches. This immediately raises the question of whether these structures correspond to tautomerization of the base pairs. Further, if unusual tautomers are indeed trapped why do they not cause errors in decoding? Here, we use molecular dynamics free energy calculations of ribosomal complexes with cognate and near-cognate tRNAs to analyze the structures and energetics of G-U mismatches in the first two codon positions. We find that the enol tautomer of G is almost isoenergetic with the corresponding ketone in the first position, while it is actually more stable in the second position. Tautomerization of U, on the other hand is highly penalized. The presence of the unusual enol form of G thus explains the crystallographic observations. However, the calculations also show that this tautomer does not cause high codon reading error frequencies, as the resulting tRNA binding free energies are significantly higher than for the cognate complex. |
| publisher |
Oxford University Press |
| publishDate |
2014 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4227757/ |
| _version_ |
1613155055903440896 |