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TitleShielding and activation of a viral membrane fusion protein.
Journal, issue, pagesNat Commun, Vol. 9, Issue 1, Page 349, Year 2018
Publish dateJan 24, 2018
AuthorsSteinar Halldorsson / Sai Li / Mengqiu Li / Karl Harlos / Thomas A Bowden / Juha T Huiskonen /
PubMed AbstractEntry 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. ...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.
External linksNat Commun / PubMed:29367607 / PubMed Central
MethodsEM (single particle) / EM (subtomogram averaging) / X-ray diffraction
Resolution1.6 - 20.0 Å
Structure data

4197

6f9b

EMDB-4197: Icosahedral reconstruction of Rift Valley fever virus virion
PDB-6f9b: Asymmetric unit of Rift Valley fever virus glycoprotein shell
Method: EM (single particle) / Resolution: 13.3 Å

4198

6f9c

EMDB-4198: Localized reconstruction of the Rift Valley fever virus glycoprotein hexamer type 1
PDB-6f9c: Model of the Rift Valley fever virus glycoprotein hexamer type 1
Method: EM (single particle) / Resolution: 8.0 Å

4199

6f9d

EMDB-4199: Localized reconstruction of the Rift Valley fever virus glycoprotein hexamer type 2
PDB-6f9d: Model of the Rift Valley fever virus glycoprotein hexamer type 2
Method: EM (single particle) / Resolution: 13.3 Å

4200

6f9e

EMDB-4200: Localized reconstruction of the Rift Valley fever virus glycoprotein hexamer type 3
PDB-6f9e: Model of the Rift Valley fever virus glycoprotein hexamer type 3
Method: EM (single particle) / Resolution: 13.3 Å

4201

6f9f

EMDB-4201: Localized reconstruction of the Rift Valley fever virus glycoprotein pentamer
PDB-6f9f: Model of the Rift Valley fever virus glycoprotein pentamer
Method: EM (single particle) / Resolution: 13.3 Å

EMDB-4202:
Subtomogram average of Rift Valley fever virus pentamer at pH 7.5
Method: EM (subtomogram averaging) / Resolution: 14.0 Å

EMDB-4203:
Subtomogram average of Rift Valley fever virus hexamer at pH 7.5
Method: EM (subtomogram averaging) / Resolution: 14.0 Å

EMDB-4204:
Subtomogram average of Rift Valley fever virus pentamer at pH 7.5 in absence of target membrane
Method: EM (subtomogram averaging) / Resolution: 17.0 Å

EMDB-4205:
Subtomogram average of Rift Valley fever virus hexamer at pH 7.5 in absence of target membrane
Method: EM (subtomogram averaging) / Resolution: 14.0 Å

EMDB-4206:
Subtomogram average of Rift Valley fever virus pentamer at pH 7.5 in presence of target membrane
Method: EM (subtomogram averaging) / Resolution: 18.0 Å

EMDB-4207:
Subtomogram average of Rift Valley fever virus hexamer at pH 7.5 in presence of target membrane
Method: EM (subtomogram averaging) / Resolution: 20.0 Å

EMDB-4208:
Subtomogram average of Rift Valley fever virus pentamer at pH 5.0 in absence of target membrane
Method: EM (subtomogram averaging) / Resolution: 20.0 Å

EMDB-4209:
Subtomogram average of Rift Valley fever virus hexamer at pH 5.0 in absence of target membrane
Method: EM (subtomogram averaging) / Resolution: 16.0 Å

EMDB-4210:
Subtomogram average of Rift Valley fever virus pentamer at pH 5.0 in presence of target membrane
Method: EM (subtomogram averaging) / Resolution: 20.0 Å

EMDB-4211:
Subtomogram average of Rift Valley fever virus hexamer at pH 5.0 in presence of target membrane
Method: EM (subtomogram averaging) / Resolution: 18.0 Å

PDB-6f8p:
Crystal structure of Gn from Rift Valley fever virus
Method: X-RAY DIFFRACTION / Resolution: 1.6 Å

Chemicals

ChemComp-HOH:
WATER / Water

Source
  • rift valley fever virus
KeywordsVIRAL PROTEIN / phlebovirus / glycoprotein / bunyavirus / host cell entry / VIRUS / enveloped virus / RVFV / fusion protein

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