Shielding and activation of a viral membrane fusion protein

DOI: 10.1038/s41467-017-02789-2

Authors: Steinar Halldorsson (Wellcome Centre for Human Genetics, University of Oxford) , Sai Li (Wellcome Centre for Human Genetics, University of Oxford) , Mengqiu Li (Wellcome Centre for Human Genetics, University of Oxford) , Karl Harlos (Wellcome Centre for Human Genetics, University of Oxford) , Thomas A. Bowden (Wellcome Centre for Human Genetics, University of Oxford) , Juha T. Huiskonen (University of Oxford)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Nature Communications , VOL 9

State: Published (Approved)
Published: January 2018
Diamond Proposal Number(s): 14744

Abstract: Entry of enveloped viruses relies on insertion of hydrophobic residues of the viral fusion protein into the host cell membrane. However, the intermediate conformations during fusion remain unknown. Here, we address the fusion mechanism of Rift Valley fever virus. We determine the crystal structure of the Gn glycoprotein and fit it with the Gc fusion protein into cryo-electron microscopy reconstructions of the virion. Our analysis reveals how the Gn shields the hydrophobic fusion loops of the Gc, preventing premature fusion. Electron cryotomography of virions interacting with membranes under acidic conditions reveals how the fusogenic Gc is activated upon removal of the Gn shield. Repositioning of the Gn allows extension of Gc and insertion of fusion loops in the outer leaflet of the target membrane. These data show early structural transitions that enveloped viruses undergo during host cell entry and indicate that analogous shielding mechanisms are utilized across diverse virus families.

Journal Keywords: Cryoelectron microscopy; Cryoelectron tomography; Viral membrane fusion; Virus structures

Diamond Keywords: Viruses; Rift Valley Fever (RVF)

Subject Areas: Biology and Bio-materials


Instruments: I03-Macromolecular Crystallography

Added On: 25/01/2018 09:20

Documents:
s41467-017-02789-2.pdf

Discipline Tags:

Pathogens Infectious Diseases Disease in the Developing World Health & Wellbeing Structural biology Life Sciences & Biotech

Technical Tags:

Diffraction Macromolecular Crystallography (MX)