Prince Stephen M, Achtman Mark, Derrick Jeremy P
Department of Biomolecular Sciences, University of Manchester Institute of Science and Technology, Sackville Street, Manchester M60 1QD, United Kingdom.
Proc Natl Acad Sci U S A. 2002 Mar 19;99(6):3417-21. doi: 10.1073/pnas.062630899. Epub 2002 Mar 12.
OpcA is an integral outer membrane protein from Neisseria meningitidis, the causative agent of meningococcal meningitis and septicemia. It mediates the adhesion of N. meningitidis to epithelial and endothelial cells by binding to vitronectin and proteoglycan cell-surface receptors. Here, we report the determination of the crystal structure of OpcA to 2.0 A resolution. OpcA adopts a 10-stranded beta-barrel structure with extensive loop regions that protrude above the predicted surface of the membrane. The second external loop adopts an unusual conformation, traversing the axis of the beta-barrel and apparently blocking formation of a pore through the membrane. Loops 2, 3, 4, and 5 associate to form one side of a crevice in the external surface of the structure, the other side being formed by loop 1. The crevice is lined by positively charged residues and would form an ideal binding site for proteoglycan polysaccharide. The structure, therefore, suggests a model for how adhesion of this important human pathogen to proteoglycan is mediated at the molecular level.
OpcA是一种来自脑膜炎奈瑟菌的整合外膜蛋白，脑膜炎奈瑟菌是脑膜炎球菌性脑膜炎和败血症的病原体。它通过与玻连蛋白和蛋白聚糖细胞表面受体结合，介导脑膜炎奈瑟菌与上皮细胞和内皮细胞的黏附。在此，我们报告了OpcA晶体结构在2.0埃分辨率下的测定结果。OpcA采用10股β桶状结构，具有广泛的环区，这些环区突出于预测的膜表面之上。第二个外环采用不寻常的构象，横穿β桶的轴，显然阻止了穿过膜的孔的形成。环2、3、4和5结合形成结构外表面缝隙的一侧，另一侧由环1形成。缝隙内衬有带正电荷的残基，将形成蛋白聚糖多糖的理想结合位点。因此，该结构提示了这种重要人类病原体在分子水平上介导与蛋白聚糖黏附的模型。
