Structure-function analyses reveal the molecular architecture and neutralization mechanism of a bacterial HEPN-MNT toxin-antitoxin system
文献类型：期刊论文
| 作者 | Yao, JY; Jia, XY; Liu, GF; Dong, YH; Wang, XX; Zhang, H; Gao, ZQ |
| 刊名 | JOURNAL OF BIOLOGICAL CHEMISTRY
 |
| 出版日期 | 2018 |
| 卷号 | 293期号:18页码:6812-6823 |
| 通讯作者 | xxwang@scsio.ac.cn ; zhangheng@ihep.ac.cn |
| 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. |
| 学科主题 | 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 |
| 源URL | [http://ir.scsio.ac.cn/handle/344004/16948]  |
| 专题 | 南海海洋研究所_中科院海洋生物资源可持续利用重点实验室 |
| 推荐引用方式 GB/T 7714 | Yao, JY,Jia, XY,Liu, GF,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 | Yao, JY.,Jia, XY.,Liu, GF.,Dong, YH.,Wang, XX.,...&Gao, ZQ.(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 | Yao, JY,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. |
入库方式： OAI收割
来源：南海海洋研究所
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