Jin Chenglong, Kang Sung-Min, Kim Do-Hee, Lee Bong-Jin
The Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Gwanak-gu, Seoul, 08826, Republic of Korea.
College of Pharmacy, Duksung Women's University, Seoul, 01369, Republic of Korea.
IUCrJ. 2021 Mar 5;8(Pt 3):362-371. doi: 10.1107/S2052252521000452. eCollection 2021 May 1.
Bacterial toxin-antitoxin (TA) systems correlate strongly with physiological processes in bacteria, such as growth arrest, survival and apoptosis. Here, the first crystal structure of a type II TA complex structure of at 2.3 Å resolution is presented. The MazEF complex consists of two MazEs and four MazFs in a heterohexameric assembly. It was estimated that MazEF forms a dodecamer with two heterohexameric MazEF complexes in solution, and a truncated complex exists in heterohexameric form. The MazE antitoxin interacts with the MazF toxin via two binding modes, namely, hydro-phobic and hydro-philic interactions. Compared with structural homologs, MazF shows distinct features in loops β1-β2, β3-β4 and β4-β5. It can be inferred that these three loops have the potential to represent the unique characteristics of MazF, especially various substrate recognition sites. In addition, MazF shows ribonuclease activity and the catalytic core of MazF lies in an RNA-binding pocket. Mutation experiments and cell-growth assays confirm Arg28 and Thr51 as critical residues for MazF ribonuclease activity. The findings shown here may contribute to the understanding of the bacterial MazEF TA system and the exploration of antimicrobial candidates to treat drug-resistant .
细菌毒素-抗毒素（TA）系统与细菌的生理过程密切相关，如生长停滞、存活和凋亡。本文展示了分辨率为2.3 Å的II型TA复合物结构的首个晶体结构。MazEF复合物由两个MazE和四个MazF组成异源六聚体组装。据估计，MazEF在溶液中与两个异源六聚体MazEF复合物形成十二聚体，并且存在截短的异源六聚体形式的复合物。MazE抗毒素通过疏水和亲水两种结合模式与MazF毒素相互作用。与结构同源物相比，MazF在β1-β2、β3-β4和β4-β5环中表现出明显特征。可以推断，这三个环有可能代表MazF的独特特性，尤其是各种底物识别位点。此外，MazF显示出核糖核酸酶活性，其催化核心位于一个RNA结合口袋中。突变实验和细胞生长测定证实Arg28和Thr51是MazF核糖核酸酶活性的关键残基。此处所示的研究结果可能有助于理解细菌的MazEF TA系统，并有助于探索治疗耐药性的抗菌候选物。
