Haemagglutinin (HA) and neuraminidase (NA) are the two main surface fusion glycoproteins embedded in the envelope of influenza viruses. The sixteen HA subtypes (H1-H16) and nine NA subtypes (N1-N9) are used to classify influenza viruses (e.g. H5N1). The antigenic variations in HA and NA enable the virus to evade host antibodies made to previous influenza strains, accounting for recurrent influenza epidemics. The HA glycoprotein is present in the viral membrane as a single polypeptide (HA0), which must be cleaved by the host's trypsin-like proteases to produce two peptides (HA1 and HA2) in order for the virus to be infectious. The type of host protease can influence the infectivity and pathogenicity of the virus.

The haemagglutinin glycoprotein is a trimer containing three structurally distinct regions: a globular head consisting of anti-parallel beta-sheets that form a beta-sandwich with a jelly-roll fold (contains the receptor binding site and the HA1/HA2 cleavage site); a triple-stranded, coiled-coil, alpha-helical stalk; and a globular foot composed of anti-parallel beta-sheets. Each monomer consists of an intact HA0 polypeptide with the HA1 and HA2 regions linked by disulphide bonds. The N-terminus of HA1 provides the central strand in the 5-stranded globular foot, while the rest of the HA1 chain makes its way to the 8-stranded globular head. HA2 provides two alpha helices, which form part of the triple-stranded coiled-coil that stabilises the trimer, its C-terminus providing the remaining strands of the 5-stranded globular foot. HA1 is less conserved among different HA subtypes, unlike HA2 which is the primary target for universal vaccines.

This superfamily represents a subdomain of the HA1 peptide that occurs following HA0 cleavage. This subdomain has an alpha/beta structure.

PMID:16178512 PMID:16543414 PMID:15475582 PMID:22231357