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-Structure paper
Title | Shielding and activation of a viral membrane fusion protein. |
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Journal, issue, pages | Nat Commun, Vol. 9, Issue 1, Page 349, Year 2018 |
Publish date | Jan 24, 2018 |
Authors | Steinar Halldorsson / Sai Li / Mengqiu Li / Karl Harlos / Thomas A Bowden / Juha T Huiskonen / |
PubMed 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. ...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 links | Nat Commun / PubMed:29367607 / PubMed Central |
Methods | EM (single particle) / EM (subtomogram averaging) / X-ray diffraction |
Resolution | 1.6 - 20.0 Å |
Structure data | EMDB-4197: Icosahedral reconstruction of Rift Valley fever virus virion EMDB-4198: Localized reconstruction of the Rift Valley fever virus glycoprotein hexamer type 1 EMDB-4199: Localized reconstruction of the Rift Valley fever virus glycoprotein hexamer type 2 EMDB-4200: Localized reconstruction of the Rift Valley fever virus glycoprotein hexamer type 3 EMDB-4201: Localized reconstruction of the Rift Valley fever virus glycoprotein pentamer EMDB-4202: EMDB-4203: EMDB-4204: EMDB-4205: EMDB-4206: EMDB-4207: EMDB-4208: EMDB-4209: EMDB-4210: EMDB-4211: PDB-6f8p: |
Chemicals | ChemComp-HOH: |
Source |
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Keywords | VIRAL PROTEIN / phlebovirus / glycoprotein / bunyavirus / host cell entry / VIRUS / enveloped virus / RVFV / fusion protein |