Fig. 4

Model for phlebovirus Gc-mediated membrane fusion. (i) In the pre-fusion state at neutral pH the Gc fusion loops (orange) are buried in the structure. (ii) At the fusion permissive pH below 5.0 (downward arrow)⁹ and upon exposure to a target membrane, the Gn moves to the side of the Gc, fully exposing the fusion loops at the tip of the Gc domain II. Consequently, full extension of Gc leads to the insertion of the fusion loops in the target membrane. (iii) The Gn–Gc dimers dissociate, allowing extended Gc monomers to redistribute on the viral membrane. (iv) After the merging of the endosomal and viral membranes, Gc adopts a trimeric post-fusion conformation (modelled in SWISS-MODEL⁶² using a phleboviral Gc post-fusion trimer PDB:5G47 as a template) where fusion loops are embedded in the fused membrane. Gn and Gc domains are coloured as in Fig. 2 and membrane is coloured in grey, with lipid head groups in darker and acyl chains in lighter shade. C-terminal part of Gc domain III that links the protein to the viral membrane is missing in the crystal structures and is indicated with blue rectangles