Figure 1. Sequence of events in membrane fusion promoted by a viral fusion protein.

Ambiguities remain in some aspects of this scheme (see main text). (a) The protein in the pre-fusion conformation, with its fusion peptide or loop (light green) sequestered. The representation is purely schematic, and various features of specific proteins are not incorporated—for example, the displacement of the N-terminal fragment of proteins that are cleaved from a precursor or the dimer-to-trimer rearrangement on the surface of flaviviruses. (b) Extended intermediate. The protein opens up, extending the fusion peptide or loop to interact with the target bilayer. The part of the protein that bears the fusion peptide forms a trimer cluster. (c) Collapse of the extended intermediate: a C-terminal segment of the protein folds back along the outside of the trimer core. The segments from the three subunits fold back independently, so that at any point in the process they can extend to different distances along the trimer axis, and the entire trimer can bow outward, away from the deforming membrane. (d) Hemifusion. When collapse of the intermediate has proceeded far enough to bring the two bilayers into contact, the apposed, proximal leaflets merge into a hemifusion stalk. (e) Fusion pore formation. As the hemifused bilayers open into a fusion pore, the final zipping up of the C-terminal ectodomain segments snaps the refolded trimer into its fully symmetric, post-fusion conformation, preventing the pore from resealing.