Structure of the dengue virus envelope protein after membrane fusion
Structure of the dengue virus envelope protein after membrane fusion
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DOI：
10.1038/nature02165
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发表时间：
2004-01-22
期刊：
影响因子：
64.8
通讯作者：
Harrison, SC
中科院分区：
文献类型：
--
作者：
Modis, Y;Ogata, S;Harrison, SC
当登革病毒的包膜糖蛋白E与受体结合，并因内体pH降低而发生构象重排时，病毒便进入宿主细胞。这种构象变化诱导病毒膜与宿主细胞膜融合。可溶性E胞外域（sE）在其三聚体融合后状态的三维结构与二聚体融合前形式存在显著差异。细长的三聚体在一端带有三个“融合环”，用于插入宿主细胞膜。它们的结构使我们能够直接模拟这些融合环如何与脂质双层相互作用。该蛋白质自身折叠，使其羧基末端指向融合环。我们提出一种融合机制，该机制由E中基本不可逆的构象变化驱动，并因融合环插入外层双层脂质小叶而促进。折叠后结构的特定特征为抑制黄病毒进入提供了策略。
Dengue virus enters a host cell when the viral envelope glycoprotein, E, binds to a receptor and responds by conformational rearrangement to the reduced pH of an endosome. The conformational change induces fusion of viral and host- cell membranes. A three- dimensional structure of the soluble E ectodomain ( sE) in its trimeric, postfusion state reveals striking differences from the dimeric, prefusion form. The elongated trimer bears three ` fusion loops' at one end, to insert into the host- cell membrane. Their structure allows us to model directly how these fusion loops interact with a lipid bilayer. The protein folds back on itself, directing its carboxy terminus towards the fusion loops. We propose a fusion mechanism driven by essentially irreversible conformational changes in E and facilitated by fusion- loop insertion into the outer bilayer leaflet. Specific features of the folded- back structure suggest strategies for inhibiting flavivirus entry.