Degenerate Connective Polypeptide 1 (CP1) Domain from Human Mitochondria! Leucyl-tRNA Synthetase

doi:10.1074/jbc.M115.672824

	Degenerate Connective Polypeptide 1 (CP1) Domain from Human Mitochondria! Leucyl-tRNA Synthetase
	Ye, Qing 1; Wang, Meng 1; Fang, Zhi-Peng 1; Ruan, Zhi-Rong 1; Ji, Quan-Quan 1; Zhou, Xiao-Long 1; Wang, En-Duo1,2
	2015-10-02
发表期刊	JOURNAL OF BIOLOGICAL CHEMISTRY
ISSN	0021-9258
卷号	290 期号:40 页码:24391-24402
发表状态	已发表
DOI	10.1074/jbc.M115.672824
摘要	The connective polypeptide 1 (CP1) editing domain of leucyltRNA synthetase (LeuRS) from various species either harbors a conserved active site to exclude tRNA mis-charging with noncognate amino acids or is evolutionarily truncated or lost because there is no requirement for high translational fidelity. However, human mitochondrial LeuRS (hmtI.euRS) contains a full-length but degenerate CP1 domain that has mutations in some residues important for post-transfer editing. The significance of such an inactive CP1 domain and a translational accuracy mechanism with different noncognate amino acids are not completely understood. Here, we identified the essential role of the evolutionarily divergent CP1 domain in facilitating hmtLeuRS's catalytic efficiency and endowing enzyme with resistance to AN2690, a broad-spectrum drug acting on LeuRSs. In addition, the canonical core of hmtLeuRS is not stringent for noncognate norvaline (Nva) and valine (Val). hmtLeuRS has a very weak tRNA-independent pre-transfer editing activity for Nva, which is insufficient to remove mis-activated Nva. Moreover, hmtLeuRS chimeras fused with a functional CP1 domain from LeuRSs of other species, regardless of origin, showed restored post-transfer editing activity and acquired fidelity during aminoacylation. This work offers a novel perspective on the role of the CP1 domain in optimizing aminoacylation efficiency.
收录类别	SCI ; EI
语种	英语
资助项目	Committee of Science and Technology in Shanghai[12JC1409700] ; Committee of Science and Technology in Shanghai[15ZR1446500]
WOS研究方向	Biochemistry & Molecular Biology
WOS类目	Biochemistry & Molecular Biology
WOS记录号	WOS:000362218900027
出版者	AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
EI入藏号	20154101356452
EI主题词	Efficiency
EI分类号	Organic Compounds:804.1 ; Production Engineering:913.1
WOS关键词	TRANSLATIONAL QUALITY-CONTROL ; ESCHERICHIA-COLI ; EDITING-DOMAIN ; AMINO-ACIDS ; AMINOACYLATION IDENTITY ; PROTEIN-BIOSYNTHESIS ; CRYSTAL-STRUCTURE ; NORVALINE ; YEAST ; SITE
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/2116
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, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, State Key Lab Mol Biol, 320 Yue Yang Rd, Shanghai, Peoples R China 2.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 200031, Peoples R China
推荐引用方式 GB/T 7714	Ye, Qing,Wang, Meng,Fang, Zhi-Peng,et al. Degenerate Connective Polypeptide 1 (CP1) Domain from Human Mitochondria! Leucyl-tRNA Synthetase[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2015,290(40):24391-24402.
APA	Ye, Qing.,Wang, Meng.,Fang, Zhi-Peng.,Ruan, Zhi-Rong.,Ji, Quan-Quan.,...&Wang, En-Duo.(2015).Degenerate Connective Polypeptide 1 (CP1) Domain from Human Mitochondria! Leucyl-tRNA Synthetase.JOURNAL OF BIOLOGICAL CHEMISTRY,290(40),24391-24402.
MLA	Ye, Qing,et al."Degenerate Connective Polypeptide 1 (CP1) Domain from Human Mitochondria! Leucyl-tRNA Synthetase".JOURNAL OF BIOLOGICAL CHEMISTRY 290.40(2015):24391-24402.