School of Molecular Bioscience, The University of Sydney, NSW, Australia.
Mol Microbiol. 2010 May;76(4):861-73. doi: 10.1111/j.1365-2958.2010.07123.x. Epub 2010 Mar 10.
Porphyromonas gingivalis is an obligately anaerobic bacterium recognized as an aetiological agent of adult periodontitis. P. gingivalis produces cysteine proteinases, the gingipains. The crystal structure of a domain within the haemagglutinin region of the lysine gingipain (Kgp) is reported here. The domain was named K2 as it is the second of three homologous structural modules in Kgp. The K2 domain structure is a 'jelly-roll' fold with two anti-parallel beta-sheets. This fold topology is shared with adhesive domains from functionally diverse receptors such as MAM domains, ephrin receptor ligand binding domains and a number of carbohydrate binding modules. Possible functions of K2 were investigated. K2 induced haemolysis of erythrocytes in a dose-dependent manner that was augmented by the blocking of anion transport. Further, cysteine-activated arginine gingipain RgpB, which degrades glycophorin A, sensitized erythrocytes to the haemolytic effect of K2. Cleaved K2, similar to that found in extracted Kgp, lacks the haemolytic activity indicating that autolysis of Kgp may be a staged process which is artificially enhanced by extraction of the protein. The data indicate a functional role for K2 in the integrated capacity conferred by Kgp to enable the porphyrin auxotroph P. gingivalis to capture essential haem from erythrocytes.
牙龈卟啉单胞菌是一种专性厌氧菌，被认为是成人牙周炎的病因。牙龈卟啉单胞菌产生半胱氨酸蛋白酶，即牙龈蛋白酶。本文报道了赖氨酸牙龈蛋白酶（Kgp）血凝素区内部结构域的晶体结构。该结构域被命名为 K2，因为它是 Kgp 中三个同源结构模块中的第二个。K2 结构域的结构是一个“果冻卷”折叠，由两个反平行的β-折叠组成。这种折叠拓扑结构与功能多样的受体的粘附结构域共享，例如 MAM 结构域、表皮生长因子受体配体结合结构域和许多碳水化合物结合模块。研究了 K2 的可能功能。K2 以剂量依赖的方式诱导红细胞溶血，阴离子转运阻断可增强这种作用。此外，激活半胱氨酸的精氨酸牙龈蛋白酶 RgpB 降解糖蛋白 A，使红细胞对 K2 的溶血作用敏感。类似于从提取的 Kgp 中发现的裂解 K2 缺乏溶血活性，表明 Kgp 的自溶可能是一个分阶段的过程，通过提取蛋白质可以人为地增强。这些数据表明 K2 在 Kgp 赋予的综合能力中具有功能作用，使卟啉营养缺陷型牙龈卟啉单胞菌能够从红细胞中捕获必需的血红素。
