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.
Highlights
Entry of enveloped viruses relies on insertion of hydrophobic residues of the viral fusion protein into the host cell membrane
Integration of our Rift Valley fever virus (RVFV) Gn with that of a previously reported RVFV Gc crystal structure into an electron cryo-microscopy reconstruction of the entire RVFV virion clarified the organization of the mature heteromeric Gn–Gc glycoprotein spike complex, revealing that the Gn shields the hydrophobic fusion loops of the Gc
Residues 154–560 were present in the RVFV Gn construct, electron density corresponding to only residues 154–469 was observed, indicating that the remaining 91 C-terminal residues were likely cleaved during a
Summary
Gn glycoprotein crystal structure reveals a novel fold. We solved the crystal structure of RVFV Gn (Fig. 1a) to 1.6-Å resolution (Supplementary Table 1). Residues 154–560 were present in the RVFV Gn construct, electron density corresponding to only residues 154–469 was observed, indicating that the remaining 91 C-terminal residues were likely cleaved during a NSm SP
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