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.

The second model proposes that the spring-loaded conformational change, the loop to helix transition of HA2 residues 55-76 (Carr and Kim, 1993; Bullough et al., 1994) , is required for fusion. This model is based on structural observations of synthetic peptides (Carr and Kim, 1993) , large fragments of HA (Bullough et al., 1994; Chen et al., 1995) and of HA in intact virions (Weber et al., 1994; Wharton et al., 1995) and in planar bilayers (Tatulian et al., 1995) . Support for the second model has also been inferred from the effects of destabilizing mutations in the coiled-coil regions of other viral glycoproteins (Buckland et al., 1992; Chen et al., 1993; Wild et al., 1994a; Reitter et al., 1995; Ramsdale et al., 1996) . We now add our findings with V55P and V55P/S71P as support for a role for the spring-loaded conformational change.