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Structure of glycosylated NPC 1 luminal domain C reveals insights into NPC 2 and Ebola virus interactions
Author(s) -
Zhao Yuguang,
Ren Jingshan,
Harlos Karl,
Stuart David I.
Publication year - 2016
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.12089
Subject(s) - ebola virus , npc1 , endosome , glycoprotein , virology , glycosylation , lipid raft , virus , biology , microbiology and biotechnology , intracellular , chemistry , receptor , biochemistry
Niemann‐pick type C1 ( NPC 1) is an endo/lysosomal membrane protein involved in intracellular cholesterol trafficking, and its luminal domain C is an essential endosomal receptor for Ebola and Marburg viruses. We have determined the crystal structure of glycosylated NPC 1 luminal domain C and find all seven possible sites are glycosylated. Mapping the disease mutations onto the glycosylated structure reveals a potential binding face for NPC 2. Knowledge‐based docking of NPC 1 onto Ebola viral glycoprotein and sequence analysis of filovirus susceptible and refractory species reveals four critical residues, H418, Q421, F502 and F504, some or all of which are likely responsible for the species‐specific susceptibility to the virus infection.