Specific Single or Double Proline Substitutions in the “Spring-loaded” Coiled-Coil Region of the Influenza Hemagglutinin Impair or Abolish Membrane Fusion Activity

Qiao, Hui; Pelletier, Sandra L.; Hoffman, Lucas; Hacker, Jill; Armstrong, R. Todd; White, Judith M.

Although we interpret our data as being consistent with the hypothesis that the spring-loaded conformational change is necessary for an early stage of fusion mediated by the influenza HA, and although related mechanisms may operate for retro-, paramyxo-, and coronavirus fusion proteins, it is unlikely that spring-loaded conformational changes activate all fusion proteins. Two well-characterized viral fusion proteins, those of Tick-borne encephalitis virus and Semliki Forest virus, either do not (Rey et al., 1995) or are not predicted (Kielian, 1995) to contain regions of high coiled-coil propensity. It will therefore be interesting to learn whether any cellular fusion proteins (Hernandez et al., 1996; Rothman, 1996) are activated by spring-loaded conformational changes. This is an intriguing question since a recently proposed model for intracellular vesicle fusion invokes coiled-coil formation between V-and T-SNAREs (Hanson et al., 1997; Weber et al., 1998) .