5F18

Structural basis of Ebola virus entry: viral glycoprotein bound to its endosomal receptor Niemann-Pick C1

Summary for 5F18

• Entry DOI: 10.2210/pdb5f18/pdb
• Related: 5F1B
• Descriptor: Niemann-Pick C1 protein (2 entities in total)
• Functional Keywords: ebola virus, glycoprotein, niemann-pick c1, transport protein
• Biological source: Homo sapiens (Human)
• Cellular location: Late endosome membrane ; Multi-pass membrane protein : O15118
• Total number of polymer chains: 1
• Total formula weight: 29436.58

Authors

Wang, H.,Shi, Y.,Song, J.,Qi, J.,Lu, G.,Yan, J.,Gao, G.F. (deposition date: 2015-11-30, release date: 2016-01-20, Last modification date: 2024-11-13)

Primary citation

Wang, H.,Shi, Y.,Song, J.,Qi, J.,Lu, G.,Yan, J.,Gao, G.F.
Ebola Viral Glycoprotein Bound to Its Endosomal Receptor Niemann-Pick C1.
Cell, 164:258-268, 2016

PubMed Abstract: 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.

PubMed: 26771495
DOI: 10.1016/j.cell.2015.12.044

Experimental method

X-RAY DIFFRACTION (2 Å)