Large Conformational Changes of Insertion 3 in Human Glycyl-tRNA Synthetase (hGlyRS) during Catalysis

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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
刊名	JOURNAL OF BIOLOGICAL CHEMISTRY
	2016
卷号	291 期号:11 页码:5740-5752
关键词	aminoacyl tRNA synthetase Charcot-Marie-Tooth disease (CMT) conformational change crystal structure enzyme mechanism
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.
中文摘要	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).
学科主题	Biochemistry & Molecular Biology
内容类型	期刊论文
源URL	[http://ir.scsio.ac.cn/handle/344004/15477]
专题	南海海洋研究所_中科院海洋生物资源可持续利用重点实验室
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, Wei.(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.