Crucial role of the C-terminal domain of Mycobacterium tuberculosis leucyl-tRNA synthetase in aminoacylation and editing

	Crucial role of the C-terminal domain of Mycobacterium tuberculosis leucyl-tRNA synthetase in aminoacylation and editing
	Hu, QH; Huang, Q; Wang, ED
刊名	NUCLEIC ACIDS RESEARCH
	2013
卷号	41 期号:3 页码:1859-1872
通讯作者	Wang, ED (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, State Key Lab Mol Biol, Ctr RNA Res,Inst Biochem & Cell Biol, Shanghai 200031, Peoples R China.,edwang@sibs.ac.cn
英文摘要	The C-terminal extension prokaryotic leucyl-tRNA synthetase (LeuRS) has been shown to make contacts with the tertiary structure base pairs of tRNA(Leu) as well as its long variable arm. However, the precise role of the flexibly linked LeuRS C-terminal domain (CTD) in aminoacylation and editing processes has not been clarified. In this study, we carried out aspartic acid scanning within the CTD of Mycobacterium tuberculosis LeuRS (MtbLeuRS) and studied the effects on tRNA(Leu)-binding capacity and enzymatic activity. Several critical residues were identified to impact upon the interactions between LeuRS and tRNA(Leu) due to their contributions in the maintenance of structural stability or a neutral interaction interface between the CTD platform and tRNA(Leu) elbow region. Moreover, we propose Arg921 as a crucial recognition site for the tRNA(Leu) long variable arm in aminoacylation and tRNA-dependent pre-transfer editing. We also show here the CTD flexibility conferred by VaI910 in regulation of LeuRS-tRNA(Leu) interaction. Taken together, our results suggest the structural importance of the CTD in modulating precise interactions between LeuRS and tRNA(Leu) during the quality control of leucyl-tRNA(Leu) synthesis. This system for the investigation of the interactions between MtbLeuRS and tRNA(Leu) provides a platform for the development of novel antitubercular drugs.
学科主题	Biochemistry & Molecular Biology
类目[WOS]	Biochemistry & Molecular Biology
关键词[WOS]	ESCHERICHIA-COLI TRNA(LEU) ; CRYSTAL-STRUCTURE ; QUALITY-CONTROL ; STRUCTURAL BASIS ; AMINO-ACIDS ; CP1 DOMAIN ; SELECTION ; SEQUENCE ; BINDING ; ENZYME
收录类别	SCI
语种	英语
WOS记录号	WOS:000316351800046
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/364]
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	Hu, QH,Huang, Q,Wang, ED. Crucial role of the C-terminal domain of Mycobacterium tuberculosis leucyl-tRNA synthetase in aminoacylation and editing[J]. NUCLEIC ACIDS RESEARCH,2013,41(3):1859-1872.
APA	Hu, QH,Huang, Q,&Wang, ED.(2013).Crucial role of the C-terminal domain of Mycobacterium tuberculosis leucyl-tRNA synthetase in aminoacylation and editing.NUCLEIC ACIDS RESEARCH,41(3),1859-1872.
MLA	Hu, QH,et al."Crucial role of the C-terminal domain of Mycobacterium tuberculosis leucyl-tRNA synthetase in aminoacylation and editing".NUCLEIC ACIDS RESEARCH 41.3(2013):1859-1872.