Li N, Collyer C A
School of Molecular Bioscience, University of Sydney NSW Australia.
Eur J Microbiol Immunol (Bp). 2011 Mar;1(1):41-58. doi: 10.1556/EuJMI.1.2011.1.7.
Gingipains, a group of arginine or lysine specific cysteine proteinases (also known as RgpA, RgpB and Kgp), have been recognized as major virulence factors in Porphyromonas gingivalis. This bacterium is one of a handful of pathogens that cause chronic periodontitis. Gingipains are involved in adherence to and colonization of epithelial cells, haemagglutination and haemolysis of erythrocytes, disruption and manipulation of the inflammatory response, and the degradation of host proteins and tissues. RgpA and Kgp are multi-domain proteins composed of catalytic domains and haemagglutinin/adhesin (HA) regions. The structure of the HA regions have previously been defined by a gingipain domain structure hypothesis which is a set of putative domain boundaries derived from the sequences of fragments of these proteins extracted from the cell surface. However, multiple sequence alignments and hidden Markov models predict an alternative domain architecture for the HA regions of gingipains. In this alternate model, two or three repeats of the so-called "cleaved adhesin" domains (and one other undefined domain in some strains) are the modules which constitute the substructure of the HA regions. Recombinant forms of these putative cleaved adhesin domains are indeed stable folded protein modules and recently determined crystal structures support the hypothesis of a modular organisation of the HA region. Based on the observed K2 and K3 structures as well as multiple sequence alignments, it is proposed that all the cleaved adhesin domains in gingipains will share the same β-sandwich jelly roll fold. The new domain model of the structure for gingipains and the haemagglutinin (HagA) proteins of P. gingivalis will guide future functional studies of these virulence factors.
牙龈蛋白酶是一组精氨酸或赖氨酸特异性半胱氨酸蛋白酶（也称为RgpA、RgpB和Kgp），已被认为是牙龈卟啉单胞菌的主要毒力因子。这种细菌是少数几种引起慢性牙周炎的病原体之一。牙龈蛋白酶参与上皮细胞的黏附与定植、红细胞的血凝和溶血、炎症反应的破坏与调控，以及宿主蛋白质和组织的降解。RgpA和Kgp是由催化结构域和血凝素/黏附素（HA）区域组成的多结构域蛋白。HA区域的结构先前已由牙龈蛋白酶结构域结构假说定义，该假说是一组从细胞表面提取的这些蛋白质片段序列推导出来的假定结构域边界。然而，多序列比对和隐马尔可夫模型预测牙龈蛋白酶HA区域存在另一种结构域架构。在这种替代模型中，所谓的“裂解黏附素”结构域的两个或三个重复序列（以及某些菌株中的另一个未定义结构域）是构成HA区域亚结构的模块。这些假定的裂解黏附素结构域的重组形式确实是稳定折叠的蛋白质模块，最近确定的晶体结构支持了HA区域模块化组织的假说。基于观察到的K2和K3结构以及多序列比对，有人提出牙龈蛋白酶中所有的裂解黏附素结构域将共享相同的β-三明治果冻卷折叠结构。牙龈蛋白酶和牙龈卟啉单胞菌血凝素（HagA）蛋白的新结构域模型将指导这些毒力因子未来的功能研究。
