Veenendaal Andreas K J, Hodgkinson Julie L, Schwarzer Lynn, Stabat David, Zenk Sebastian F, Blocker Ariel J
Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK.
Mol Microbiol. 2007 Mar;63(6):1719-30. doi: 10.1111/j.1365-2958.2007.05620.x.
Type III secretion systems (T3SSs) are essential virulence determinants of many Gram-negative bacterial pathogens. The Shigella T3SS consists of a cytoplasmic bulb, a transmembrane region and a hollow 'needle' protruding from the bacterial surface. Physical contact with host cells initiates secretion and leads to assembly of a pore, formed by IpaB and IpaC, in the host cell membrane, through which proteins that facilitate host cell invasion are translocated. As the needle is implicated in host cell sensing and secretion regulation, its tip should contain components that initiate host cell contact. Through biochemical and immunological studies of wild-type and mutant Shigella T3SS needles, we reveal tip complexes of differing compositions and functional states, which appear to represent the molecular events surrounding host cell sensing and pore formation. Our studies indicate that the interaction between IpaB and IpaD at needle tips is key to host cell sensing, orchestration of IpaC secretion and its subsequent assembly at needle tips. This allows insertion into the host cell membrane of a translocation pore that is continuous with the needle.
III型分泌系统（T3SSs）是许多革兰氏阴性细菌病原体的重要毒力决定因素。志贺氏菌T3SS由一个细胞质球、一个跨膜区域和一个从细菌表面突出的中空“针”组成。与宿主细胞的物理接触引发分泌，并导致由IpaB和IpaC在宿主细胞膜中形成一个孔，促进宿主细胞入侵的蛋白质通过该孔转运。由于“针”与宿主细胞感知和分泌调节有关，其尖端应包含启动宿主细胞接触的成分。通过对野生型和突变型志贺氏菌T3SS“针”的生化和免疫学研究，我们揭示了不同组成和功能状态的尖端复合物，它们似乎代表了围绕宿主细胞感知和孔形成的分子事件。我们的研究表明，IpaB和IpaD在“针”尖端的相互作用是宿主细胞感知、IpaC分泌的协调及其随后在“针”尖端组装的关键。这允许将与“针”连续的转运孔插入宿主细胞膜。
