Ebola Viral Glycoprotein Bound to Its Endosomal Receptor Niemann-Pick C1.
Cell
; 164(1-2): 258-268, 2016 Jan 14.
Article
em En
| MEDLINE
| ID: mdl-26771495
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.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Glicoproteínas de Membrana
/
Proteínas de Transporte
/
Proteínas do Envelope Viral
/
Ebolavirus
Limite:
Humans
Idioma:
En
Revista:
Cell
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
China