https://ror.org/00rcxh774 Institute for Genetics, University of Cologne, Cologne, Germany
https://ror.org/00rcxh774 Institute of Biochemistry, University of Cologne, Cologne, Germany.
Life Sci Alliance. 2023 Dec 13;7(2). doi: 10.26508/lsa.202302422. Print 2024 Feb.
Intracellular bacteria are threatened by ubiquitin-mediated autophagy, whenever the bacterial surface or enclosing membrane structures become targets of host ubiquitin ligases. As a countermeasure, many intracellular pathogens encode deubiquitinase (DUB) effectors to keep their surfaces free of ubiquitin. Most bacterial DUBs belong to the OTU or CE-clan families. The betaproteobacteria and , causative agents of melioidosis and glanders, respectively, encode the TssM effector, the only known bacterial DUB belonging to the USP class. TssM is much shorter than typical eukaryotic USP enzymes and lacks the canonical ubiquitin-recognition region. By solving the crystal structures of isolated TssM and its complex with ubiquitin, we found that TssM lacks the entire "Fingers" subdomain of the USP fold. Instead, the TssM family has evolved the functionally analog "Littlefinger" loop, which is located towards the end of the USP domain and recognizes different ubiquitin interfaces than those used by USPs. The structures revealed the presence of an N-terminal immunoglobulin-fold domain, which is able to form a strand-exchange dimer and might mediate TssM localization to the bacterial surface.
细胞内细菌受到泛素介导的自噬的威胁，当细菌表面或包膜结构成为宿主泛素连接酶的靶标时。作为一种对策，许多细胞内病原体编码去泛素化酶 (DUB) 效应子，以保持其表面无泛素化。大多数细菌 DUB 属于 OTU 或 CE 家族。β-变形菌和 ，分别是类鼻疽和鼻疽的病原体，编码 TssM 效应子，这是唯一已知属于 USP 类的细菌 DUB。TssM 比典型的真核 USP 酶短得多，并且缺乏典型的泛素识别区域。通过解决分离的 TssM 及其与泛素的复合物的晶体结构，我们发现 TssM 缺乏 USP 折叠的整个“手指”亚结构域。相反，TssM 家族已经进化出功能类似的“小手指”环，它位于 USP 结构域的末端，识别与 USPs 不同的泛素界面。这些结构揭示了存在一个 N 端免疫球蛋白折叠结构域，它能够形成链交换二聚体，并可能介导 TssM 定位于细菌表面。
