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

DOI: 10.1002/1873-3468.12089 DOI Help
PMID: 26846330 PMID Help

Authors: Yuguang Zhao (University of Oxford) , Jingshan Ren (University of Oxford) , Karl Harlos (Wellcome Trust Centre for Human Genetics, University of Oxford) , Dave Stuart (Diamond Light Source; University of Oxford)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Febs Letters , VOL 590 (5) , PAGES 605-12

State: Published (Approved)
Published: February 2016

Open Access Open Access

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 Keywords: Cholesterol transport; Ebola virus receptor; Ebola virus susceptibility; Niemann–Pick disease type C; NPC1; NPC2

Subject Areas: Biology and Bio-materials

Instruments: I04-Macromolecular Crystallography

Added On: 24/02/2016 10:31

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