Figure 2.

Membrane fusion by class II envelope proteins. (a) The protein forms dimers in the outer protein shell of the virion. The “stem-anchor” (cyan) tethers the protein to the viral membrane. Gc from Rift Valley fever virus (RVFV) is shown as an example [5^••]. (b) The protein responds to the reduced pH of an endosomal compartment with a hinge motion that exposes the hydrophobic fusion loop (orange). The fusion loop inserts into the cell membrane. A crystal structure of RVFV Gc proposed to correspond to this “prehairpin” intermediate is shown [5^••]. (c) The protein then folds back on itself, directing the fusion loop toward the transmembrane anchor. The refolding energy bends the apposed membranes. Creation of additional trimer contacts between the stem-anchor and the ectodomain leads to fusion of the viral and cellular membranes. The postfusion conformation of dengue type 2 virus is shown [41].