|Hemagglutinin (HA) is the most abundant of the three integral membrane proteins in the viral envelope of influenza and is responsible for both binding and fusion. At low pH within the endosome, HA undergoes large conformational changes that lead to fusion between the envelope and endosomal membrane, thereby allowing the viral nucleocapsid to pass into the cytosol.
This motion represents a ~20 stretch of non-polar, relatively well conserved amino acids at the N-terminal domain of HA. At both pHs, the domain is a kinked, predominantly helical amphipathic structure. At the fusogenic pH 5, however, the domain has a sharper bend, an additional 3-10-helix and a twist, resulting in the repositioning of Glu 15 and Asp 19 relative to that at the nonfusogenic pH 7.4. Rotation of these charged residues out of the membrane plane creates a hydrophobic pocket that allows a deeper insertion of the fusion domain into the core of the lipid bilayer. |