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Large Conformational Changes of Insertion 3 in Human Glycyl-tRNA Synthetase (hGlyRS) during Catalysis
Deng, Xiangyu; Qin, Xiangjing; Chen, Lei; Jia, Qian; Zhang, Yonghui; Zhang, Zhiyong; Lei, Dongsheng; Ren, Gang; Zhou, Zhihong; Wang, Zhong; Li, Qing; Xie, Wei; Xie, W (reprint author), Sun Yat Sen Univ, Sch Life Sci, State Key Lab Biocontrol, 135 West Xingang Rd, Guangzhou 510275, Guangdong, Peoples R China.
2016
Source PublicationJOURNAL OF BIOLOGICAL CHEMISTRY
Volume291Issue:11Pages:5740-5752
AbstractGlycyl-tRNA synthetase (GlyRS) is the enzyme that covalently links glycine to cognate tRNA for translation. It is of great research interest because of its nonconserved quaternary structures, unique species-specific aminoacylation properties, and noncanonical functions in neurological diseases, but none of these is fully understood. We report two crystal structures of human GlyRS variants, in the free form and in complex with tRNA(Gly) respectively, and reveal new aspects of the glycylation mechanism. We discover that insertion 3 differs considerably in conformation in catalysis and that it acts like a switch and fully opens to allow tRNA to bind in a cross-subunit fashion. The flexibility of the protein is supported by molecular dynamics simulation, as well as enzymatic activity assays. The biophysical and biochemical studies suggest that human GlyRS may utilize its flexibility for both the traditional function (regulate tRNA binding) and alternative functions (roles in diseases).
Department[Deng, Xiangyu; Chen, Lei; Jia, Qian; Zhou, Zhihong; Xie, Wei] Sun Yat Sen Univ, Sch Life Sci, State Key Lab Biocontrol, 135 West Xingang Rd, Guangzhou 510275, Guangdong, Peoples R China; [Deng, Xiangyu; Chen, Lei; Jia, Qian; Zhou, Zhihong; Wang, Zhong; Li, Qing; Xie, Wei] Sun Yat Sen Univ, Ctr Cellular & Struct Biol, Guangzhou 510006, Guangdong, Peoples R China; [Wang, Zhong; Li, Qing] Sun Yat Sen Univ, Sch Pharmaceut Sci, Guangzhou 510006, Guangdong, Peoples R China; [Qin, Xiangjing] Chinese Acad Sci, South China Sea Inst, Guangzhou 510301, Guangdong, Peoples R China; [Zhang, Yonghui; Zhang, Zhiyong] Univ Sci & Technol China, Hefei Natl Lab Phys Sci Microscale, Hefei 230026, Anhui, Peoples R China; [Zhang, Yonghui; Zhang, Zhiyong] Univ Sci & Technol China, Sch Life Sci, Hefei 230026, Anhui, Peoples R China; [Lei, Dongsheng; Ren, Gang] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Mol Foundry, Berkeley, CA 94720 USA ; LMB
KeywordAminoacyl Trna Synthetase Charcot-marie-tooth Disease (Cmt) Conformational Change Crystal Structure Enzyme Mechanism
Subject AreaBiochemistry & Molecular Biology
Document Type期刊论文
Identifierhttp://ir.scsio.ac.cn/handle/344004/15477
Collection中科院海洋生物资源可持续利用重点实验室
Corresponding AuthorXie, W (reprint author), Sun Yat Sen Univ, Sch Life Sci, State Key Lab Biocontrol, 135 West Xingang Rd, Guangzhou 510275, Guangdong, Peoples R China.
Recommended Citation
GB/T 7714
Deng, Xiangyu,Qin, Xiangjing,Chen, Lei,et al. Large Conformational Changes of Insertion 3 in Human Glycyl-tRNA Synthetase (hGlyRS) during Catalysis[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2016,291(11):5740-5752.
APA Deng, Xiangyu.,Qin, Xiangjing.,Chen, Lei.,Jia, Qian.,Zhang, Yonghui.,...&Xie, W .(2016).Large Conformational Changes of Insertion 3 in Human Glycyl-tRNA Synthetase (hGlyRS) during Catalysis.JOURNAL OF BIOLOGICAL CHEMISTRY,291(11),5740-5752.
MLA Deng, Xiangyu,et al."Large Conformational Changes of Insertion 3 in Human Glycyl-tRNA Synthetase (hGlyRS) during Catalysis".JOURNAL OF BIOLOGICAL CHEMISTRY 291.11(2016):5740-5752.
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