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Role of tRNA amino acid-accepting end in aminoacylation and its quality control
Aminoacyl–tRNA synthetases (aaRSs) are remarkable enzymes that are in charge of the accurate recognition and ligation of amino acids and tRNA molecules. The greatest difficulty in accurate aminoacylation appears to be in discriminating between highly similar amino acids. To reduce mischarging of tRN...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3203616/ https://www.ncbi.nlm.nih.gov/pubmed/21775341 http://dx.doi.org/10.1093/nar/gkr595 |
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author | Zhou, Xiao-Long Du, Dao-Hai Tan, Min Lei, Hui-Yan Ruan, Liang-Liang Eriani, Gilbert Wang, En-Duo |
author_facet | Zhou, Xiao-Long Du, Dao-Hai Tan, Min Lei, Hui-Yan Ruan, Liang-Liang Eriani, Gilbert Wang, En-Duo |
author_sort | Zhou, Xiao-Long |
collection | PubMed |
description | Aminoacyl–tRNA synthetases (aaRSs) are remarkable enzymes that are in charge of the accurate recognition and ligation of amino acids and tRNA molecules. The greatest difficulty in accurate aminoacylation appears to be in discriminating between highly similar amino acids. To reduce mischarging of tRNAs by non-cognate amino acids, aaRSs have evolved an editing activity in a second active site to cleave the incorrect aminoacyl–tRNAs. Editing occurs after translocation of the aminoacyl–CCA(76) end to the editing site, switching between a hairpin and a helical conformation for aminoacylation and editing. Here, we studied the consequence of nucleotide changes in the CCA(76) accepting end of tRNA(Leu) during the aminoacylation and editing reactions. The analysis showed that the terminal A(76) is essential for both reactions, suggesting that critical interactions occur in the two catalytic sites. Substitutions of C(74) and C(75) selectively decreased aminoacylation keeping nearly unaffected editing. These mutations might favor the regular helical conformation required to reach the editing site. Mutating the editing domain residues that contribute to CCA(76) binding reduced the aminoacylation fidelity leading to cell-toxicity in the presence of non-cognate amino acids. Collectively, the data show how protein synthesis quality is controlled by the CCA(76) homogeneity of tRNAs. |
format | Online Article Text |
id | pubmed-3203616 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-32036162011-10-28 Role of tRNA amino acid-accepting end in aminoacylation and its quality control Zhou, Xiao-Long Du, Dao-Hai Tan, Min Lei, Hui-Yan Ruan, Liang-Liang Eriani, Gilbert Wang, En-Duo Nucleic Acids Res Nucleic Acid Enzymes Aminoacyl–tRNA synthetases (aaRSs) are remarkable enzymes that are in charge of the accurate recognition and ligation of amino acids and tRNA molecules. The greatest difficulty in accurate aminoacylation appears to be in discriminating between highly similar amino acids. To reduce mischarging of tRNAs by non-cognate amino acids, aaRSs have evolved an editing activity in a second active site to cleave the incorrect aminoacyl–tRNAs. Editing occurs after translocation of the aminoacyl–CCA(76) end to the editing site, switching between a hairpin and a helical conformation for aminoacylation and editing. Here, we studied the consequence of nucleotide changes in the CCA(76) accepting end of tRNA(Leu) during the aminoacylation and editing reactions. The analysis showed that the terminal A(76) is essential for both reactions, suggesting that critical interactions occur in the two catalytic sites. Substitutions of C(74) and C(75) selectively decreased aminoacylation keeping nearly unaffected editing. These mutations might favor the regular helical conformation required to reach the editing site. Mutating the editing domain residues that contribute to CCA(76) binding reduced the aminoacylation fidelity leading to cell-toxicity in the presence of non-cognate amino acids. Collectively, the data show how protein synthesis quality is controlled by the CCA(76) homogeneity of tRNAs. Oxford University Press 2011-11 2011-07-20 /pmc/articles/PMC3203616/ /pubmed/21775341 http://dx.doi.org/10.1093/nar/gkr595 Text en © The Author(s) 2011. Published by Oxford University Press. http://creativecommons.org/licenses/by-nc/3.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Nucleic Acid Enzymes Zhou, Xiao-Long Du, Dao-Hai Tan, Min Lei, Hui-Yan Ruan, Liang-Liang Eriani, Gilbert Wang, En-Duo Role of tRNA amino acid-accepting end in aminoacylation and its quality control |
title | Role of tRNA amino acid-accepting end in aminoacylation and its quality control |
title_full | Role of tRNA amino acid-accepting end in aminoacylation and its quality control |
title_fullStr | Role of tRNA amino acid-accepting end in aminoacylation and its quality control |
title_full_unstemmed | Role of tRNA amino acid-accepting end in aminoacylation and its quality control |
title_short | Role of tRNA amino acid-accepting end in aminoacylation and its quality control |
title_sort | role of trna amino acid-accepting end in aminoacylation and its quality control |
topic | Nucleic Acid Enzymes |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3203616/ https://www.ncbi.nlm.nih.gov/pubmed/21775341 http://dx.doi.org/10.1093/nar/gkr595 |
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