The mechanism of discriminative aminoacylation by isoleucyl-tRNA synthetase based on wobble nucleotide recognition
Abstract The faithful charging of amino acids to cognate tRNAs by aminoacyl-tRNA synthetases (AARSs) determines the fidelity of protein translation. Isoleucyl-tRNA synthetase (IleRS) distinguishes tRNAIle from tRNAMet solely based on the nucleotide at wobble position (N34), and a single substitution...
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Nature Portfolio
2024-12-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-55183-0 |
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| author | Bingyi Chen Fang Yi Zhiteng Luo Feihu Lu Hongwei Liu Siting Luo Qiong Gu Huihao Zhou |
| author_facet | Bingyi Chen Fang Yi Zhiteng Luo Feihu Lu Hongwei Liu Siting Luo Qiong Gu Huihao Zhou |
| author_sort | Bingyi Chen |
| collection | DOAJ |
| description | Abstract The faithful charging of amino acids to cognate tRNAs by aminoacyl-tRNA synthetases (AARSs) determines the fidelity of protein translation. Isoleucyl-tRNA synthetase (IleRS) distinguishes tRNAIle from tRNAMet solely based on the nucleotide at wobble position (N34), and a single substitution at N34 could exchange the aminoacylation specificity between two tRNAs. Here, we report the structural and biochemical mechanism of N34 recognition-based tRNA discrimination by Saccharomyces cerevisiae IleRS (ScIleRS). ScIleRS utilizes a eukaryotic/archaeal-specific arginine as the H-bond donor to recognize the common carbonyl group (H-bond acceptor) of various N34s of tRNAIle, which induces mutual structural adaptations between ScIleRS and tRNAIle to achieve a preferable editing state. C34 of unmodified tRNAIle(CAU) (behaves like tRNAMet) lacks a relevant H-bond acceptor, which disrupts key H-bonding interactions and structural adaptations and suspends the ScIleRS·tRNAIle(CAU) complex in an initial non-reactive state. This wobble nucleotide recognition-based structural adaptation provides mechanistic insights into selective tRNA aminoacylation by AARSs. |
| format | Article |
| id | doaj-art-fe5a7bef30bb46ab9e96b2d21bb91769 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Nature Portfolio |
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| series | Nature Communications |
| spelling | doaj-art-fe5a7bef30bb46ab9e96b2d21bb917692025-01-05T12:34:51ZengNature PortfolioNature Communications2041-17232024-12-0115111110.1038/s41467-024-55183-0The mechanism of discriminative aminoacylation by isoleucyl-tRNA synthetase based on wobble nucleotide recognitionBingyi Chen0Fang Yi1Zhiteng Luo2Feihu Lu3Hongwei Liu4Siting Luo5Qiong Gu6Huihao Zhou7State Key Laboratory of Anti-Infective Drug Discovery and Development, School of Pharmaceutical Sciences, Sun Yat-sen UniversityState Key Laboratory of Anti-Infective Drug Discovery and Development, School of Pharmaceutical Sciences, Sun Yat-sen UniversityState Key Laboratory of Anti-Infective Drug Discovery and Development, School of Pharmaceutical Sciences, Sun Yat-sen UniversityState Key Laboratory of Anti-Infective Drug Discovery and Development, School of Pharmaceutical Sciences, Sun Yat-sen UniversityDepartment of Laboratory Medicine, The Affiliated Qingyuan Hospital (Qingyuan People’s Hospital), Guangzhou Medical UniversityState Key Laboratory of Anti-Infective Drug Discovery and Development, School of Pharmaceutical Sciences, Sun Yat-sen UniversityState Key Laboratory of Anti-Infective Drug Discovery and Development, School of Pharmaceutical Sciences, Sun Yat-sen UniversityState Key Laboratory of Anti-Infective Drug Discovery and Development, School of Pharmaceutical Sciences, Sun Yat-sen UniversityAbstract The faithful charging of amino acids to cognate tRNAs by aminoacyl-tRNA synthetases (AARSs) determines the fidelity of protein translation. Isoleucyl-tRNA synthetase (IleRS) distinguishes tRNAIle from tRNAMet solely based on the nucleotide at wobble position (N34), and a single substitution at N34 could exchange the aminoacylation specificity between two tRNAs. Here, we report the structural and biochemical mechanism of N34 recognition-based tRNA discrimination by Saccharomyces cerevisiae IleRS (ScIleRS). ScIleRS utilizes a eukaryotic/archaeal-specific arginine as the H-bond donor to recognize the common carbonyl group (H-bond acceptor) of various N34s of tRNAIle, which induces mutual structural adaptations between ScIleRS and tRNAIle to achieve a preferable editing state. C34 of unmodified tRNAIle(CAU) (behaves like tRNAMet) lacks a relevant H-bond acceptor, which disrupts key H-bonding interactions and structural adaptations and suspends the ScIleRS·tRNAIle(CAU) complex in an initial non-reactive state. This wobble nucleotide recognition-based structural adaptation provides mechanistic insights into selective tRNA aminoacylation by AARSs.https://doi.org/10.1038/s41467-024-55183-0 |
| spellingShingle | Bingyi Chen Fang Yi Zhiteng Luo Feihu Lu Hongwei Liu Siting Luo Qiong Gu Huihao Zhou The mechanism of discriminative aminoacylation by isoleucyl-tRNA synthetase based on wobble nucleotide recognition Nature Communications |
| title | The mechanism of discriminative aminoacylation by isoleucyl-tRNA synthetase based on wobble nucleotide recognition |
| title_full | The mechanism of discriminative aminoacylation by isoleucyl-tRNA synthetase based on wobble nucleotide recognition |
| title_fullStr | The mechanism of discriminative aminoacylation by isoleucyl-tRNA synthetase based on wobble nucleotide recognition |
| title_full_unstemmed | The mechanism of discriminative aminoacylation by isoleucyl-tRNA synthetase based on wobble nucleotide recognition |
| title_short | The mechanism of discriminative aminoacylation by isoleucyl-tRNA synthetase based on wobble nucleotide recognition |
| title_sort | mechanism of discriminative aminoacylation by isoleucyl trna synthetase based on wobble nucleotide recognition |
| url | https://doi.org/10.1038/s41467-024-55183-0 |
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