Structure-function analyses reveal the molecular architecture and neutralization mechanism of a bacterial HEPN-MNT toxin-antitoxin system
Jia, XY; Yao, JY; Gao, ZQ; Liu, GF; Dong, YH; Wang, XX; Zhang, H; xxwang@scsio.ac.cn; zhangheng@ihep.ac.cn
2018
发表期刊JOURNAL OF BIOLOGICAL CHEMISTRY
卷号293期号:18页码:6812-6823
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.
部门归属[Jia, Xuanyan] Anhui Univ, Inst Phys Sci & Informat Technol, Hefei 230601, Anhui, Peoples R China; [Yao, Jianyun; Wang, Xiaoxue] Chinese Acad Sci, South China Sea Inst Oceanol, Guangdong Key Lab Marine Mat Med, CAS Key Lab Trop Marine Bioresources & Ecol, Guangzhou 510301, Guangdong, Peoples R China; [Gao, Zengqiang; Dong, Yu-Hui; Zhang, Heng] Chinese Acad Sci, Inst High Energy Phys, Beijing Synchrotron Radiat Facil, Beijing 100049, Peoples R China; [Liu, Guangfeng] Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, Natl Ctr Prot Sci Shanghai, Shanghai 200031, Peoples R China
学科领域Biochemistry & Molecular Biology
关键词[WOS]toxin ; crystal structure ; small-angle X-ray scattering (SAXS) ; RNA binding protein ; RNA-protein interaction ; RNA ribonuclease ; toxin-antitoxin system
资助项目LMB
文献类型期刊论文
条目标识符http://ir.scsio.ac.cn/handle/344004/16948
专题中科院海洋生物资源可持续利用重点实验室
通讯作者xxwang@scsio.ac.cn; zhangheng@ihep.ac.cn
推荐引用方式
GB/T 7714
Jia, XY,Yao, JY,Gao, ZQ,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 Jia, XY.,Yao, JY.,Gao, ZQ.,Liu, GF.,Dong, YH.,...&zhangheng@ihep.ac.cn.(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 Jia, XY,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.
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