Identification of Lethal Mutations in Yeast Threonyl-tRNA Synthetase Revealing Critical Residues in Its Human Homolog

	Identification of Lethal Mutations in Yeast Threonyl-tRNA Synthetase Revealing Critical Residues in Its Human Homolog
	Ruan, ZR; Fang, ZP; Ye, Q; Lei, HY; Eriani, G; Zhou, XL; Wang, ED
刊名	JOURNAL OF BIOLOGICAL CHEMISTRY
	2015
卷号	290 期号:3 页码:1664-1678
通讯作者	Zhou, XL (reprint author), Chinese Acad Sci, State Key Lab Mol Biol, Inst Biochem & Cell Biol, Ctr RNA Res,Shanghai Inst Biol Sci, 320 Yue Yang Rd, Shanghai 200031, Peoples R China.,xlzhou@sibcb.ac.cn ; edwang@sibcb.ac.cn
英文摘要	Aminoacyl-tRNA synthetases (aaRSs) are a group of ancient enzymes catalyzing aminoacylation and editing reactions for protein biosynthesis. Increasing evidence suggests that these critical enzymes are often associated with mammalian disorders. Therefore, complete determination of the enzymes functions is essential for informed diagnosis and treatment. Here, we show that a yeast knock-out strain for the threonyl-tRNA synthetase (ThrRS) gene is an excellent platform for such an investigation. Saccharomyces cerevisiae ThrRS has a unique modular structure containing four structural domains and a eukaryote-specific N-terminal extension. Using randomly mutated libraries of the ThrRS gene (thrS) and a genetic screen, a set of loss-of-function mutants were identified. The mutations affected the synthetic and editing activities and influenced the dimer interface. The results also highlighted the role of the N-terminal extension for enzymatic activity and protein stability. To gain insights into the pathological mechanisms induced by mutated aaRSs, we systematically introduced the loss-of-function mutations into the human cytoplasmic ThrRS gene. All mutations induced similar detrimental effects, showing that the yeast model could be used to study pathology-associated point mutations in mammalian aaRSs.
学科主题	Biochemistry & Molecular Biology
类目[WOS]	Biochemistry & Molecular Biology
关键词[WOS]	C-TERMINAL DOMAIN ; ESCHERICHIA-COLI ; QUALITY-CONTROL ; ACTIVE-SITE ; AMINO-ACID ; AMINOACYLATION REACTION ; RANDOM MUTAGENESIS ; BINDING DOMAIN ; ZINC ION ; PROTEIN
收录类别	SCI
语种	英语
WOS记录号	WOS:000348056400033
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/43]
专题	上海生化细胞研究所_上海生科院生化细胞研究所
推荐引用方式 GB/T 7714	Ruan, ZR,Fang, ZP,Ye, Q,et al. Identification of Lethal Mutations in Yeast Threonyl-tRNA Synthetase Revealing Critical Residues in Its Human Homolog[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2015,290(3):1664-1678.
APA	Ruan, ZR.,Fang, ZP.,Ye, Q.,Lei, HY.,Eriani, G.,...&Wang, ED.(2015).Identification of Lethal Mutations in Yeast Threonyl-tRNA Synthetase Revealing Critical Residues in Its Human Homolog.JOURNAL OF BIOLOGICAL CHEMISTRY,290(3),1664-1678.
MLA	Ruan, ZR,et al."Identification of Lethal Mutations in Yeast Threonyl-tRNA Synthetase Revealing Critical Residues in Its Human Homolog".JOURNAL OF BIOLOGICAL CHEMISTRY 290.3(2015):1664-1678.