A SPRING-LOADED MECHANISM FOR THE CONFORMATIONAL CHANGE OF INFLUENZA HEMAGGLUTININ

Influenza hemagglutinin (HA) undergoes a conformational change that in duces viral fusion with the cellular membrane. The structure of HA in the fusogenic state is unknown. We have identified a sequence in HA th at has a high propensity for forming a coiled coil. Surprisingly, this sequence corresponds to a loop region in the X-ray structure of nativ e HA: the loop is followed by a three-stranded, coiled-coil stem. We f ind that a 36 residue peptide (LOOP-36), comprising the loop region an d the first part of the stem, forms a three-stranded coiled coil. This coiled coll is extended and stabilized in a longer peptide, correspon ding to LOOP-36 plus the residues of a preceding, short alpha helix. T hese findings lead to a model for the fusogenic conformation of HA: th e coiled-coil stem of the native state extends, relocating the hydroph obic fusion peptide, by 100 angstrom, toward the target membrane.