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Shielding and activation of a viral membrane fusion protein.

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.
Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1038/s41467-017-02789-2

Authors

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Institution:
University of Oxford
Division:
Medical Sciences Division
Department:
NDM; NDM Experimental Medicine
Role:
Author
More by this author
Institution:
University of Oxford
Division:
Medical Sciences Division
Department:
NDM; Human Genetics Wt Centre
Role:
Author
ORCID:
0000-0002-9353-0355
More by this author
Institution:
University of Oxford
Division:
Medical Sciences Division
Department:
NDM; Structural Biology
Role:
Author
More by this author
Institution:
University of Oxford
Division:
Medical Sciences Division
Department:
NDM; Structural Biology
Role:
Author
More by this author
Institution:
University of Oxford
Division:
MSD
Department:
NDM
Sub department:
Structural Biology
Role:
Author
ORCID:
0000-0002-8066-8785


Publisher:
Nature Publishing Group
Journal:
Nature Communications More from this journal
Volume:
9
Issue:
1
Pages:
349
Publication date:
2018-01-01
Acceptance date:
2017-12-28
DOI:
EISSN:
2041-1723
ISSN:
2041-1723
Pmid:
29367607


Language:
English
Keywords:
Pubs id:
pubs:821518
UUID:
uuid:fc712bc3-1fec-4da7-a5a7-8a8e9758fcac
Local pid:
pubs:821518
Deposit date:
2018-01-29
ARK identifier:

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