Structures of the conformations assumed by HA during the virus life cycle.

<p>Trimeric HA molecule is shown as a ribbon diagram, with the HA₁ subunit colored in blue, the HA₂ subunit colored in red, and residues corresponding to the fusion peptide colored in yellow. (<b>A</b>) The site within the trimeric HA molecule that acts as a substrate for activating protease (i.e. the cleavage loop) is denoted with an arrow. (<b>B</b>) Upon proteolytic activation within the cleavage loop, the N-terminus of the newly generated HA₂ subunit is relocated to the trimer interior where it forms extensive contacts with a network of residues within the fusion peptide pocket. This forms the metastable conformation that is primed for fusion. (<b>C</b>) Upon exposure to low pH, the HA undergoes a series of conformational changes that result in the extrusion of the fusion peptide for mediating membrane fusion between the virion and endosomal membranes.