Title: Grapnels of the Influenza Virus: The hemagglutinin fusion domain's structure and function in curving and fusing membranes on infection
Abstract: The N-terminus of the influenza hemagglutinin HA2 subunit, known as the fusion domain or fusion peptide, is critical to membrane fusion and influenza cellular entry. It is one of the most conserved sequences in the influenza genome such that modest mutation can arrest membrane fusion. Despite this domain’s critical role to influenza membrane fusion and entry, there is no clear consensus in the literature on this domain’s function. Research over the last 25 years focused on a fusiogenic 20-residue peptide of this domain, which adopts a boomerang structure with an N-terminal α-helix and a partially disordered C-terminus. We recently demonstrated that a peptide extending an additional three completely conserved, hydrophobic residues was needed to accurately model the fusion domain’s structure. The full-length fusion domain is more fusiogenic and adopts a distinct and unique helical- hairpin membrane protein fold. The helical-hairpin is stabilized by four aliphatic CαHα—O hydrogen bonds as well as a charge-dipole interaction at the N-terminus. We show that the helical-hairpin structure's wedge shape helps promote negative membrane curvature, which could play an important role in stabilizing the high-energy intermediates of membrane fusion.
Cm-Bio 11-19 Lorieau