Robb Craig S, Robb Melissa, Nano Francis E, Boraston Alisdair B
Department of Biochemistry and Microbiology, University of Victoria, Victoria, BC V8W 3P6, Canada.
Department of Biochemistry and Microbiology, University of Victoria, Victoria, BC V8W 3P6, Canada.
Structure. 2016 Feb 2;24(2):277-84. doi: 10.1016/j.str.2015.11.012. Epub 2015 Dec 31.
Tse2 is a cytoactive toxin secreted by a type six secretion apparatus of Pseudomonas aeruginosa. The Tse2 toxin naturally attacks a target in the cytoplasm of bacterial cells, and can cause toxicity if artificially introduced into eukaryotic cells. The X-ray crystal structure of the complex of Tse2 and its cognate immunity protein Tsi2 revealed a heterotetrameric structure with an extensive binding interface. Structural identity was found between Tse2 and NAD-dependent enzymes, especially ADP-ribosylating toxins, which facilitated the identification of the Tse2 active site and revealed it to be occluded upon binding the inhibitor Tsi2. The structural identity shared with NAD-dependent enzymes, including conserved catalytic residues, suggests that the mechanism of Tse2 toxicity may be NAD dependent.
Tse2是一种由铜绿假单胞菌的六型分泌系统分泌的细胞活性毒素。Tse2毒素天然攻击细菌细胞胞质中的靶点，如果人工导入真核细胞则可导致毒性。Tse2与其同源免疫蛋白Tsi2复合物的X射线晶体结构显示出具有广泛结合界面的异源四聚体结构。发现Tse2与NAD依赖性酶，尤其是ADP-核糖基化毒素之间存在结构同一性，这有助于鉴定Tse2活性位点，并揭示其在结合抑制剂Tsi时被封闭。与NAD依赖性酶共有的结构同一性，包括保守的催化残基，表明Tse2毒性机制可能是NAD依赖性的。
