PDF(Pubmed)
Abstract：
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 Burkholderia pseudomallei and Burkholderia mallei, 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.
摘要：
细胞内细菌受到泛素介导的自噬的威胁，每当细菌表面或封闭的膜结构成为宿主泛素连接酶的目标时。作为对策,许多细胞内病原体编码去泛素酶（DUB）效应子，以保持其表面无泛素。大多数细菌DUB属于OTU或CE氏族家族。假伯克霍尔德菌和伯克霍尔德菌，melioidosis和腺体的病原体，分别,编码TssM效应器，唯一已知的属于USP类的细菌DUB。TssM比典型的真核USP酶短得多，并且缺乏经典的泛素识别区域。通过求解分离的TssM及其与泛素的复合物的晶体结构，我们发现TssM缺少USP折叠的整个“手指”子域。相反，TssM家族已经进化出功能模拟的“小指头”循环，它位于USP域的末端，识别与USP使用的泛素接口不同的泛素接口。该结构揭示了N末端免疫球蛋白折叠结构域的存在，能够形成链交换二聚体并且可能介导TssM定位到细菌表面。
