Modis Yorgo, Ogata Steven, Clements David, Harrison Stephen C
Howard Hughes Medical Institute, Children's Hospital and Harvard Medical School, 320 Longwood Avenue, Boston, MA 02115, USA.
Proc Natl Acad Sci U S A. 2003 Jun 10;100(12):6986-91. doi: 10.1073/pnas.0832193100. Epub 2003 May 20.
Dengue virus is an emerging global health threat. Its major envelope glycoprotein, E, mediates viral attachment and entry by membrane fusion. A crystal structure of the soluble ectodomain of E from dengue virus type 2 reveals a hydrophobic pocket lined by residues that influence the pH threshold for fusion. The pocket, which accepts a hydrophobic ligand, opens and closes through a conformational shift in a beta-hairpin at the interface between two domains. These features point to a structural pathway for the fusion-activating transition and suggest a strategy for finding small-molecule inhibitors of dengue and other flaviviruses.
登革病毒是一种新出现的全球健康威胁。其主要包膜糖蛋白E通过膜融合介导病毒的附着和进入。来自2型登革病毒的E的可溶性胞外域的晶体结构揭示了一个由影响融合pH阈值的残基排列的疏水口袋。该口袋可容纳一个疏水配体,通过两个结构域之间界面处β-发夹结构的构象变化来打开和关闭。这些特征指出了融合激活转变的结构途径,并提出了寻找登革病毒和其他黄病毒小分子抑制剂的策略。