Structure-function analyses reveal the molecular architecture and neutralization mechanism of a bacterial HEPN-MNT toxin-antitoxin system

doi:10.1074/jbc.RA118.002421

	Structure-function analyses reveal the molecular architecture and neutralization mechanism of a bacterial HEPN-MNT toxin-antitoxin system
	Liu, GF; Jia, XY; Yao, JY; Gao ZQ(高增强); Dong YH(董宇辉); Zhang H(张衡); Gao, ZQ; Dong, YH; Wang, XX; Zhang, H
刊名	JOURNAL OF BIOLOGICAL CHEMISTRY
	2018
卷号	293 期号:18 页码:6812-6823
关键词	toxin crystal structure small-angle X-ray scattering (SAXS) RNA binding protein RNA-protein interaction RNA ribonuclease toxin-antitoxin system
ISSN号	0021-9258
DOI	10.1074/jbc.RA118.002421
文献子类	Article
英文摘要	Toxin-antitoxin (TA) loci in bacteria are small genetic modules that regulate various cellular activities, including cell growth and death. The two-gene module encoding a HEPN (higher eukaryotes and prokaryotes nucleotide-binding) domain and a cognate MNT (minimal nucleotidyltransferase) domain have been predicted to represent a novel type II TA system prevalent in archaea and bacteria. However, the neutralization mechanism and cellular targets of the TA family remain unclear. The toxin SO_3166 having a HEPN domain and its cognate antitoxin SO_3165 with an MNT domain constitute a typical type II TA system that regulates cell motility and confers plasmid stability in the bacterium Shewanella oneidensis. Here, we report the crystal structure and solution conformation of the SO_3166-SO_3165 pair, representing the first complex structures in this TA family. The structures revealed that SO_3165 and SO_3166 form a tight heterooctamer (at a 2:6 ratio), an organization that is very rare in other TA systems. We also observed that SO_3166 dimerization enables the formation of a deep cleft at the HEPN-domain interface harboring a composite RX4-6H active site that functions as an RNA-cleaving RNase. SO_3165 bound SO_3166 mainly through its two -helices (2 and 4), functioning as molecular recognition elements. Moreover, their insertion into the SO_3166 cleft sterically blocked the RX4-6H site or narrowed the cleft to inhibit RNA substrate binding. Structure-based mutagenesis confirmed the important roles of these -helices in SO_3166 binding and inhibition. Our structure-function analysis provides first insights into the neutralization mechanism of the HEPN-MNT TA family.
电子版国际标准刊号	1083-351X
WOS关键词	RAY SOLUTION SCATTERING ; SMALL-ANGLE SCATTERING ; HAEMOPHILUS-INFLUENZAE ; ESCHERICHIA-COLI ; STRESS-RESPONSE ; DOMAIN ; NUCLEOTIDYLTRANSFERASE ; SOFTWARE ; IDENTIFICATION ; PROTEINS
WOS研究方向	Biochemistry & Molecular Biology
语种	英语
WOS记录号	WOS:000431487300016
内容类型	期刊论文
源URL	[http://ir.ihep.ac.cn/handle/311005/285885]
专题	高能物理研究所_多学科研究中心高能物理研究所_粒子天体物理中心
通讯作者	Zhang H(张衡)
作者单位	中国科学院高能物理研究所
推荐引用方式 GB/T 7714	Liu, GF,Jia, XY,Yao, JY,et al. Structure-function analyses reveal the molecular architecture and neutralization mechanism of a bacterial HEPN-MNT toxin-antitoxin system[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2018,293(18):6812-6823.
APA	Liu, GF.,Jia, XY.,Yao, JY.,高增强.,董宇辉.,...&Zhang, H.(2018).Structure-function analyses reveal the molecular architecture and neutralization mechanism of a bacterial HEPN-MNT toxin-antitoxin system.JOURNAL OF BIOLOGICAL CHEMISTRY,293(18),6812-6823.
MLA	Liu, GF,et al."Structure-function analyses reveal the molecular architecture and neutralization mechanism of a bacterial HEPN-MNT toxin-antitoxin system".JOURNAL OF BIOLOGICAL CHEMISTRY 293.18(2018):6812-6823.