Relationships between protein domains and lipid monolayers in membrane fusion

The hemagglutinin (HA) of influenza virus is the prototypic viral fusion protein. The possible roles of each domain of HA in fusion are presented. Specifically, it is proposed that the ectodomain causes hemifusion, the transmembrane domain causes fusion pore formation, and the cytoplasmic tail causes pore flickering. Lipids must also participate in fusion. Pores are created in stable hemifusion diaphragms by increasing the spontaneous curvature of inner monolayers of membranes to be more positive, but further increase in spontaneous curvature does not promote pore growth. In contrast, increasing spontaneous curvature of inner leaflets does promote pore enlargement for wild type HA, demonstrating that there is a lipid component to pore growth.