Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan.
PLoS Pathog. 2010 Oct 7;6(10):e1001129. doi: 10.1371/journal.ppat.1001129.
The Dot/Icm type IVB secretion system (T4BSS) is a pivotal determinant of Legionella pneumophila pathogenesis. L. pneumophila translocate more than 100 effector proteins into host cytoplasm using Dot/Icm T4BSS, modulating host cellular functions to establish a replicative niche within host cells. The T4BSS core complex spanning the inner and outer membranes is thought to be made up of at least five proteins: DotC, DotD, DotF, DotG and DotH. DotH is the outer membrane protein; its targeting depends on lipoproteins DotC and DotD. However, the core complex structure and assembly mechanism are still unknown. Here, we report the crystal structure of DotD at 2.0 Å resolution. The structure of DotD is distinct from that of VirB7, the outer membrane lipoprotein of the type IVA secretion system. In contrast, the C-terminal domain of DotD is remarkably similar to the N-terminal subdomain of secretins, the integral outer membrane proteins that form substrate conduits for the type II and the type III secretion systems (T2SS and T3SS). A short β-segment in the otherwise disordered N-terminal region, located on the hydrophobic cleft of the C-terminal domain, is essential for outer membrane targeting of DotH and Dot/Icm T4BSS core complex formation. These findings uncover an intriguing link between T4BSS and T2SS/T3SS.
Dot/Icm 型 IVB 分泌系统（T4BSS）是嗜肺军团菌发病机制的关键决定因素。嗜肺军团菌使用 Dot/Icm T4BSS 将超过 100 种效应蛋白易位到宿主细胞质中，从而调节宿主细胞功能，在宿主细胞内建立复制龛。跨越内膜和外膜的 T4BSS 核心复合物被认为至少由五种蛋白质组成：DotC、DotD、DotF、DotG 和 DotH。DotH 是外膜蛋白；其靶向依赖于脂蛋白 DotC 和 DotD。然而，核心复合物的结构和组装机制仍然未知。在这里，我们报道了 DotD 的晶体结构，分辨率为 2.0Å。DotD 的结构与 IVA 型分泌系统的外膜脂蛋白 VirB7 不同。相比之下，DotD 的 C 末端结构域与分泌体的 N 末端亚结构域非常相似，分泌体是形成 II 型和 III 型分泌系统（T2SS 和 T3SS）底物通道的完整外膜蛋白。在 otherwise disordered N 末端区域中，位于 C 末端结构域疏水裂缝上的一个短 β 片段对于 DotH 和 Dot/Icm T4BSS 核心复合物形成的外膜靶向至关重要。这些发现揭示了 T4BSS 和 T2SS/T3SS 之间的有趣联系。
