Evdokimov A G, Anderson D E, Routzahn K M, Waugh D S
Protein Engineering Section Macromolecular Crystallography Laboratory, National Cancer Institute at Frederick, Frederick, MD 21702-1201, USA.
J Mol Biol. 2001 Sep 28;312(4):807-21. doi: 10.1006/jmbi.2001.4973.
Many Gram-negative bacterial pathogens employ a contact-dependent (type III) secretion system to deliver effector proteins into the cytosol of animal or plant cells. Collectively, these effectors enable the bacteria to evade the immune response of the infected organism by modulating host-cell functions. YopM, a member of the leucine-rich repeat protein superfamily, is an effector produced by the bubonic plague bacterium, Yersinia pestis, that is essential for virulence. Here, we report crystal structures of YopM at 2.4 and 2.1 A resolution. Among all leucine-rich repeat family members whose atomic coordinates have been reported, the repeating unit of YopM has the least canonical secondary structure. In both crystals, four YopM monomers form a hollow cylinder with an inner diameter of 35 A. The domain that targets YopM for translocation into eukaryotic cells adopts a well-ordered, alpha-helical conformation that packs tightly against the proximal leucine-rich repeat module. A similar alpha-helical domain can be identified in virulence-associated leucine-rich repeat proteins produced by Salmonella typhimurium and Shigella flexneri, and in the conceptual translation products of several open reading frames in Y. pestis.
许多革兰氏阴性细菌病原体利用接触依赖性（III型）分泌系统将效应蛋白输送到动物或植物细胞的胞质溶胶中。总体而言，这些效应蛋白使细菌能够通过调节宿主细胞功能来逃避受感染生物体的免疫反应。YopM是富含亮氨酸重复蛋白超家族的成员，是由鼠疫杆菌耶尔森氏菌产生的一种效应蛋白，对毒力至关重要。在此，我们报告了分辨率为2.4 Å和2.1 Å的YopM晶体结构。在所有已报道原子坐标的富含亮氨酸重复家族成员中，YopM的重复单元具有最少的典型二级结构。在这两种晶体中，四个YopM单体形成一个内径为35 Å的空心圆柱体。将YopM转运到真核细胞中的结构域采用了一种有序的α螺旋构象，紧密堆积在近端富含亮氨酸的重复模块上。在鼠伤寒沙门氏菌和福氏志贺氏菌产生的与毒力相关的富含亮氨酸重复蛋白以及鼠疫耶尔森氏菌中几个开放阅读框的概念翻译产物中，可以鉴定出类似的α螺旋结构域。
