A spring-loaded mechanism for the conformational change of influenza hemagglutinin.
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abstract
Influenza hemagglutinin (HA) undergoes a conformational change that induces viral fusion with the cellular membrane. The structure of HA in the fusogenic state is unknown. We have identified a sequence in HA that has a high propensity for forming a coiled coil. Surprisingly, this sequence corresponds to a loop region in the X-ray structure of native HA: the loop is followed by a three-stranded, coiled-coil stem. We find that a 36 residue peptide (LOOP-36), comprising the loop region and the first part of the stem, forms a three-stranded coiled coil. This coiled coil is extended and stabilized in a longer peptide, corresponding to LOOP-36 plus the residues of a preceding, short alpha helix. These findings lead to a model for the fusogenic conformation of HA: the coiled-coil stem of the native state extends, relocating the hydrophobic fusion peptide, by 100 A, toward the target membrane.