Membrane fusion is blocked by mutations in the HA leash region (right).
White/Macmillan
For HA, interactions between a nonhelical region and a trimer of helices cause fusion. Using mutational analyses, the group shows that fusion requires contacts between a long chain, which they call the leash, near the viral membrane with the helices near the target membrane (usually a host endosome as the virus escapes into the cytoplasm). They suggest that packing of the leash into the grooves of the helices condenses HA, thus bringing together viral and host membranes. “There's nothing holy about helix–helix interactions as a means to pull membranes together,” says White. “You can do it with other types of interactions.” This may help explain why class II viral fusion proteins work although they do not have a lot of helical structure. ▪
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