Title : Structural studies of the hemagglutinin-membrane interaction
Abstract:
The viral fusion protein hemagglutinin (HA) is the predominant influenza surface glycoprotein and mediates engagement with and entry into host cells. Influenza A virus HAs are categorised into two broad and immunologically distinct phylogenetic groups. Group 2 HA subtypes include H3, which is found in a large proportion of seasonal influenzas, and H7, which is present in some highly pathogenic avian influenzas.
HA is a single-pass, type I transmembrane protein and exists as a trimeric assembly on the surface of the influenza virus. Viral membrane fusion is induced through large, and relatively well characterised, conformational changes in the HA ectodomain. In contrast, very little is known about the architecture of HA’s interaction with the phospholipid bilayer — a crucial element of the viral fusion machinery . To date, the only structural information about HA’s transmembrane domain is derived from a group 1, H1 subtype in the pre-fusion conformation.
Through purification of group 2 HAs in lipid environments, followed by single particle analysis cryoEM, we have resolved the first structures of full-length post-fusion HA. These provide mechanistic insights into the architecture of the transmembrane domain of group 2 HAs, as well as the mode of interaction of HA’s highly conserved fusion peptide with membrane.
