Deane Janet E, Roversi Pietro, King Carole, Johnson Steven, Lea Susan M
Sir William Dunn School of Pathology, South Parks Rd, University of Oxford, Oxford OX1 3RE, UK.
J Mol Biol. 2008 Apr 4;377(4):985-92. doi: 10.1016/j.jmb.2008.01.072. Epub 2008 Feb 4.
Many Gram-negative pathogenic bacteria use a complex macromolecular machine, known as the type 3 secretion system (T3SS), to transfer virulence proteins into host cells. The T3SS is composed of a cytoplasmic bulb, a basal body spanning the inner and outer bacterial membranes, and an extracellular needle. Secretion is regulated by both cytoplasmic and inner membrane proteins that must respond to specific signals in order to ensure that virulence proteins are not secreted before contact with a eukaryotic cell. This negative regulation is mediated, in part, by a family of proteins that are thought to physically block the entrance to the secretion apparatus until an appropriate signal is received following host cell contact. Despite weak sequence homology between proteins of this family, the crystal structures of Shigella flexneri MxiC we present here confirm the conservation of domain topology with the homologue from Yersinia sp. Interestingly, comparison of the Shigella and Yersinia structures reveals a significant structural change that results in substantial domain re-arrangement and opening of one face of the molecule. The conservation of a negatively charged patch on this face suggests it may have a role in binding other components of the T3SS.
许多革兰氏阴性病原菌利用一种称为Ⅲ型分泌系统（T3SS）的复杂大分子机器将毒力蛋白转运到宿主细胞中。Ⅲ型分泌系统由一个胞质球、一个跨越细菌内膜和外膜的基体以及一根胞外针组成。分泌过程受胞质蛋白和内膜蛋白调控，这些蛋白必须对特定信号作出反应，以确保毒力蛋白在与真核细胞接触之前不会被分泌。这种负调控部分由一类蛋白质介导，这类蛋白质被认为会在物理上阻断分泌装置的入口，直到宿主细胞接触后接收到适当信号。尽管该家族蛋白质之间的序列同源性较弱，但我们在此展示的福氏志贺菌MxiC的晶体结构证实了其与耶尔森氏菌同源物在结构域拓扑结构上的保守性。有趣的是，对志贺菌和耶尔森氏菌结构的比较揭示了一个显著的结构变化，该变化导致了结构域的大量重排以及分子一侧表面的开放。该表面上一个带负电荷区域的保守性表明它可能在结合Ⅲ型分泌系统的其他组分中发挥作用。
