Structure of glycosylated NPC1 luminal domain C reveals insights into NPC2 and Ebola virus interactions.

Abstract:

:Niemann-pick type C1 (NPC1) 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 NPC1 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 NPC2. Knowledge-based docking of NPC1 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.

journal_name

FEBS Lett

journal_title

FEBS letters

authors

Zhao Y,Ren J,Harlos K,Stuart DI

doi

10.1002/1873-3468.12089

subject

Has Abstract

pub_date

2016-03-01 00:00:00

pages

605-12

issue

5

eissn

0014-5793

issn

1873-3468

journal_volume

590

pub_type

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