Terradot Laurent, Bayliss Richard, Oomen Clasien, Leonard Gordon A, Baron Christian, Waksman Gabriel
Institute of Structural Molecular Biology, Malet Street, London WC1E 7HX, UK.
Proc Natl Acad Sci U S A. 2005 Mar 22;102(12):4596-601. doi: 10.1073/pnas.0408927102. Epub 2005 Mar 11.
Type IV secretion systems (T4SSs) are commonly used secretion machineries in Gram-negative bacteria. They are used in the infection of human, animal, or plant cells and the propagation of antibiotic resistance. The T4SS apparatus spans both membranes of the bacterium and generally is composed of 12 proteins, named VirB1-11 and VirD4 after proteins of the canonical Agrobacterium tumefaciens T4SS. The periplasmic core complex of VirB8/VirB10 structurally and functionally links the cytoplasmic NTPases of the system with its outer membrane and pilus components. Here we present crystal structures of VirB8 of Brucella suis, the causative agent of brucellosis, and ComB10, a VirB10 homolog of Helicobacter pylori, the causative agent of gastric ulcers. The structures of VirB8 and ComB10 resemble known folds, albeit with novel secondary-structure modifications unique to and conserved within their respective families. Both proteins crystallized as dimers, providing detailed predictions about their self associations. These structures make a substantial contribution to the repertoire of T4SS component structures and will serve as springboards for future functional and protein-protein interaction studies by using knowledge-based site-directed and deletion mutagenesis.
IV型分泌系统（T4SSs）是革兰氏阴性菌中常用的分泌机制。它们用于感染人类、动物或植物细胞以及传播抗生素耐药性。T4SS装置跨越细菌的两层膜，通常由12种蛋白质组成，根据典型的根癌土壤杆菌T4SS的蛋白质命名为VirB1 - 11和VirD4。VirB8/VirB10的周质核心复合物在结构和功能上把系统的细胞质NTP酶与其外膜和菌毛成分联系起来。在这里，我们展示了猪布鲁氏菌（布鲁氏菌病的病原体）的VirB8以及幽门螺杆菌（胃溃疡的病原体）的VirB10同源物ComB10的晶体结构。VirB8和ComB10的结构类似于已知的折叠结构，尽管有各自家族特有的且保守的新型二级结构修饰。这两种蛋白质均以二聚体形式结晶，为它们的自我缔合提供了详细预测。这些结构对T4SS组件结构库有重大贡献，并将通过基于知识的定点和缺失诱变，为未来的功能和蛋白质 - 蛋白质相互作用研究提供跳板。
