title: Class II fusion proteins.
abstract: Enveloped viruses rely on fusion proteins in their envelope to fuse the viral membrane to the host-cell membrane. This key step in viral entry delivers the viral genome into the cytoplasm for replication. Although class II fusion proteins are genetically and structurally unrelated to class I fusion proteins, they use the same physical principles and topology as other fusion proteins to drive membrane fusion. Exposure of a fusion loop first allows it to insert into the host-cell membrane. Conserved hydrophobic residues in the fusion loop act as an anchor, which penetrates only partway into the outer bilayer leaflet of the host-cell membrane. Subsequent folding back of the fusion protein on itself directs the C-terminal viral transmembrane anchor towards the fusion loop. This fold-back forces the host-cell membrane (held by the fusion loop) and the viral membrane (held by the C-terminal transmembrane anchor) against each other, resulting in membrane fusion. In class II fusion proteins, the fold-back is triggered by the reduced pH of an endosome, and is accompanied by the assembly of fusion protein monomers into trimers. The fold-back occurs by domain rearrangement rather than by an extensive refolding of secondary structure, but this domain rearrangement and the assembly of monomers into trimers together bury a large surface area. The energy that is thus released exerts a bending force on the apposed viral and cellular membranes, causing them to bend towards each other and, eventually, to fuse.
authors.affiliation: Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, USA. yorgo.modis@yale.edu
authors.forename: Yorgo
authors.initials: Y
authors.lastname: Modis
mesh_terms: D000818:Animals; D006801:Humans; D008561:Membrane Fusion; D011487:Protein Conformation; D014760:Viral Fusion Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000502:physiology*
chemical_list: D014760:Viral Fusion Proteins