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

doi:10.1074/jbc.M114.599886

	Identification of Lethal Mutations in Yeast Threonyl-tRNA Synthetase Revealing Critical Residues in Its Human Homolog
	Ruan, Zhi-Rong 1; Fang, Zhi-Peng 1; Ye, Qing 1; Lei, Hui-Yan 1; Eriani, Gilbert 3; Zhou, Xiao-Long 1; Wang, En-Duo1,2
	2015-01-16
发表期刊	JOURNAL OF BIOLOGICAL CHEMISTRY
ISSN	1083351X
卷号	290 期号:3 页码:1664-1678
发表状态	已发表
DOI	10.1074/jbc.M114.599886
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.
收录类别	SCI ; EI
语种	英语
资助项目	Committee of Science and Technology in Shanghai[12JC1409700]
WOS研究方向	Biochemistry & Molecular Biology
WOS类目	Biochemistry & Molecular Biology
WOS记录号	WOS:000348056400033
出版者	AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
EI入藏号	20150400449949
EI主题词	Amino acids ; Biochemistry ; Enzymes ; Genes ; Mammals ; Proteins
EI分类号	Biological Materials and Tissue Engineering:461.2 ; Biochemistry:801.2 ; Organic Compounds:804.1 ; Agricultural Equipment and Methods; Vegetation and Pest Control:821
WOS关键词	C-TERMINAL DOMAIN ; ESCHERICHIA-COLI ; AMINO-ACID ; ACTIVE-SITE ; RANDOM MUTAGENESIS ; ZINC ION ; AMINOACYLATION ; BINDING ; PROTEIN ; ATP
原始文献类型	Article
引用统计
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/2269
专题	生命科学与技术学院_特聘教授组_王恩多组
通讯作者	Zhou, Xiao-Long
作者单位	1.Chinese Acad Sci, State Key Lab Mol Biol, Inst Biochem & Cell Biol, Ctr RNA Res,Shanghai Inst Biol Sci, Shanghai 200031, Peoples R China 2.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 200031, Peoples R China 3.Univ Strasbourg, CNRS, Inst Biol Mol & Cellulaire, Architecture & React ARN, F-67084 Strasbourg, France
推荐引用方式 GB/T 7714	Ruan, Zhi-Rong,Fang, Zhi-Peng,Ye, Qing,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, Zhi-Rong.,Fang, Zhi-Peng.,Ye, Qing.,Lei, Hui-Yan.,Eriani, Gilbert.,...&Wang, En-Duo.(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, Zhi-Rong,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.