The Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul, Republic of Korea.
MasterMediTech, Seoul, Republic of Korea.
Nat Commun. 2024 Nov 24;15(1):10188. doi: 10.1038/s41467-024-54551-0.
HEPN-MNT, a type VII TA module, comprises the HEPN toxin and the MNT antitoxin, which acts as a nucleotidyltransferase that transfers the NMP moiety to the corresponding HEPN toxin, thereby interfering with its toxicity. Here, we report crystal structures of the Legionella pneumophila HEPN-MNT module, including HEPN, AMPylated HEPN, MNT, and the HEPN-MNT complex. Our structural analysis and biochemical assays, suggest that HEPN is a metal-dependent RNase and identify its active site residues. We also elucidate the oligomeric state of HEPN in solution. Interestingly, L. pneumophila MNT, which lacks a long C-terminal α4 helix, controls the toxicity of HEPN toxin via a distinct binding mode with HEPN. Finally, we propose a comprehensive regulatory mechanism of the L. pneumophila HEPN-MNT module based on structural and functional studies. These results provide insight into the type VII HEPN-MNT TA system.
HEPN-MNT，一种 VII 型 TA 模块，由 HEPN 毒素和 MNT 解毒素组成，后者作为核苷酸转移酶，将 NMP 部分转移到相应的 HEPN 毒素上，从而干扰其毒性。在这里，我们报告了嗜肺军团菌 HEPN-MNT 模块的晶体结构，包括 HEPN、AMPylated HEPN、MNT 和 HEPN-MNT 复合物。我们的结构分析和生化分析表明，HEPN 是一种金属依赖性 RNA 酶，并确定了其活性位点残基。我们还阐明了 HEPN 在溶液中的寡聚状态。有趣的是，缺乏长 C 端 α4 螺旋的嗜肺军团菌 MNT 通过与 HEPN 结合的独特模式来控制 HEPN 毒素的毒性。最后，我们基于结构和功能研究提出了一个关于嗜肺军团菌 HEPN-MNT 模块的综合调控机制。这些结果为 VII 型 HEPN-MNT TA 系统提供了深入的了解。
