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
发表期刊JOURNAL OF BIOLOGICAL CHEMISTRY
卷号291期号:11页码:5740-5752
摘要Glycyl-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).
部门归属[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
关键词Aminoacyl Trna Synthetase Charcot-marie-tooth Disease (Cmt) Conformational Change Crystal Structure Enzyme Mechanism
学科领域Biochemistry & Molecular Biology
文献类型期刊论文
条目标识符http://ir.scsio.ac.cn/handle/344004/15477
专题中科院海洋生物资源可持续利用重点实验室
通讯作者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.
推荐引用方式
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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