Nitrosative stress inhibits aminoacylation and editing activities of mitochondrial threonyl-tRNA synthetase by S-nitrosation

doi:10.1093/nar/gkaa471

	Nitrosative stress inhibits aminoacylation and editing activities of mitochondrial threonyl-tRNA synthetase by S-nitrosation
	Zheng, WQ1,2,3 ; Zhang, YY 4; Yao, Q 4; Chen, YZ 4; Qiao, XH 4; Wang, ED1,2,3 ; Chen, C 3,4,5; Zhou, XL 1,3
	2020-07-09
发表期刊	NUCLEIC ACIDS RESEARCH (IF:16.6[JCR-2023],16.1[5-Year])
ISSN	0305-1048
EISSN	1362-4962
卷号	48 期号:12 页码:6799-6810
发表状态	已发表
DOI	10.1093/nar/gkaa471
摘要	Structure and/or function of proteins are frequently affected by oxidative/nitrosative stress via posttranslational modifications. Aminoacyl-tRNA synthetases (aaRSs) constitute a class of ubiquitously expressed enzymes that control cellular protein homeostasis. Here, we found the activity of human mitochondrial (mt) threonyl-tRNA synthetase (hmtThrRS) is resistant to oxidative stress (H2O2) but profoundly sensitive to nitrosative stress (S-nitrosoglutathione, GSNO). Further study showed four Cys residues in hmtThrRS were modified by S-nitrosation upon GSNO treatment, and one residue was one of synthetic active sites. We analyzed the effect of modification at individual Cys residue on aminoacylation and editing activities of hmtThrRS in vitro and found that both activities were decreased. We further confirmed that S-nitrosation of mtThrRS could be readily detected in vivo in both human cells and various mouse tissues, and we systematically identified dozens of S-nitrosation-modified sites in most aaRSs, thus establishing both mitochondrial and cytoplasmic aaRS species with S-nitrosation ex vivo and in vivo, respectively. Interestingly, a decrease in the S-nitrosation modification level of mtThrRS was observed in a Huntington disease mouse model. Overall, our results establish, for the first time, a comprehensive S-nitrosation-modified aaRS network and a previously unknown mechanism on the basis of the inhibitory effect of S-nitrosation on hmtThrRS.
关键词	PROTEIN-SYNTHESIS QUALITY-CONTROL NUCLEAR EXPORT NITRIC-OXIDE MECHANISM COMPLEX PHOSPHORYLATION SUSCEPTIBILITY MISTRANSLATION NITROSYLATION
URL	查看原文
收录类别	SCI ; SCIE
语种	英语
WOS研究方向	Biochemistry & Molecular Biology
WOS类目	Biochemistry & Molecular Biology
WOS记录号	WOS:000574288800035
出版者	OXFORD UNIV PRESS, GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/123428
专题	生命科学与技术学院生命科学与技术学院_特聘教授组_王恩多组生命科学与技术学院_博士生
通讯作者	Wang, ED; Chen, C
作者单位	1.Chinese Acad Sci, Ctr Excellence Mol Cell Sci, Shanghai Inst Biochem & Cell Biol, State Key Lab Mol Biol, Shanghai 200031, Peoples R China 2.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China 3.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 4.Chinese Acad Sci, CAS Ctr Excellence Biomacromol, Inst Biophys, Natl Lab Biomacromol, Beijing 100101, Peoples R China 5.Capital Med Univ, Beijing Inst Brain Disorders, Beijing 100069, Peoples R China
第一作者单位	生命科学与技术学院
通讯作者单位	生命科学与技术学院
推荐引用方式 GB/T 7714	Zheng, WQ,Zhang, YY,Yao, Q,et al. Nitrosative stress inhibits aminoacylation and editing activities of mitochondrial threonyl-tRNA synthetase by S-nitrosation[J]. NUCLEIC ACIDS RESEARCH,2020,48(12):6799-6810.
APA	Zheng, WQ.,Zhang, YY.,Yao, Q.,Chen, YZ.,Qiao, XH.,...&Zhou, XL.(2020).Nitrosative stress inhibits aminoacylation and editing activities of mitochondrial threonyl-tRNA synthetase by S-nitrosation.NUCLEIC ACIDS RESEARCH,48(12),6799-6810.
MLA	Zheng, WQ,et al."Nitrosative stress inhibits aminoacylation and editing activities of mitochondrial threonyl-tRNA synthetase by S-nitrosation".NUCLEIC ACIDS RESEARCH 48.12(2020):6799-6810.