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Ebola Viral Glycoprotein Bound to Its Endosomal Receptor Niemann-Pick C1

Filoviruses, including Ebola and Marburg, cause fatal hemorrhagic fever in humans and primates. Understanding      how these viruses enter host cells could help to develop effective therapeutics. An endosomal protein, Niemann-Pick C1 (NPC1), has been identified as a necessary entry receptor for this process, and priming of the viral  glycoprotein (GP) to a fusion-competent state is a prerequisite for NPC1 binding. Here, we have determined the crystal structure of the primed GP (GPcl) of Ebola virus bound to domain C of NPC1 (NPC1-C) at a resolution of 2.3 Å. NPC1-C utilizes two protruding loops to engage a hydrophobic cavity on head of GPcl. Upon enzymatic  cleavage and NPC1-C binding, conformational change in the GPcl further affects the state of the internal fusion   loop, triggering membrane fusion. Our data therefore provide structural insights into filovirus entry in the late endosome and the molecular basis for design of therapeutic inhibitors of viral entry.The research was conducted at    the BL17U1 and BL19U1 beamline of the SSRF.