Kaufmann Bärbel, Nybakken Grant E, Chipman Paul R, Zhang Wei, Diamond Michael S, Fremont Daved H, Kuhn Richard J, Rossmann Michael G
Department of Biological Sciences, Purdue University, 915 West State Street, West Lafayette, IN 47907-2054, USA.
Proc Natl Acad Sci U S A. 2006 Aug 15;103(33):12400-4. doi: 10.1073/pnas.0603488103. Epub 2006 Aug 8.
Flaviviruses, such as West Nile virus (WNV), are significant human pathogens. The humoral immune response plays an important role in the control of flavivirus infection and disease. The structure of WNV complexed with the Fab fragment of the strongly neutralizing mAb E16 was determined to 14.5-Angstrom resolution with cryo-electron microscopy. E16, an antibody with therapeutic potential, binds to domain III of the WNV envelope glycoprotein. Because of steric hindrance, Fab E16 binds to only 120 of the 180 possible binding sites on the viral surface. Fitting of the previously determined x-ray structure of the Fab-domain III complex into the cryo-electron microscopy density required a change of the elbow angle between the variable and constant domains of the Fab. The structure suggests that the E16 antibody neutralizes WNV by blocking the initial rearrangement of the E glycoprotein before fusion with a cellular membrane.
黄病毒,如西尼罗河病毒(WNV),是重要的人类病原体。体液免疫反应在控制黄病毒感染和疾病方面发挥着重要作用。利用冷冻电子显微镜技术,以14.5埃的分辨率确定了与强中和性单克隆抗体E16的Fab片段复合的西尼罗河病毒的结构。具有治疗潜力的抗体E16与西尼罗河病毒包膜糖蛋白的结构域III结合。由于空间位阻,Fab E16仅与病毒表面180个可能结合位点中的120个结合。将先前确定的Fab-结构域III复合物的x射线结构拟合到冷冻电子显微镜密度图中,需要改变Fab可变区和恒定区之间的肘角。该结构表明,E16抗体通过在与细胞膜融合之前阻断E糖蛋白的初始重排来中和西尼罗河病毒。