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 not abolished in fusion activity, the single Pro mutant, V55P, displayed a significantly reduced rate of lipid mixing ‫%08-06ف(‬ inhibited compared with wt-HA). V55P is also impaired in content mixing and syncytia formation. We hypothesize that the impairment in the rate of lipid mixing reflects a reduction in the rate or extent with which V55P undergoes the loop to helix transition of HA2 residues 55-76, as opposed to its noted structural differences compared with wt-HA at pH 7 (Table III) . We propose this because the mutant L80P has similar alterations in pH 7 structure, yet still induces lipid (and apparently content) mixing with the same efficiency and pH dependence as wt-HA.