Hemagglutinins (alternatively spelt haemagglutinin, from the Greek haima, 'blood' + Latin gluten, 'glue') are homotrimeric glycoproteins present on the protein capsids of viruses in the Paramyxoviridae and Orthomyxoviridae families.
[1][2][3] Hemagglutinins are responsible for binding to receptors, sialic acid residues, on host cell membranes to initiate virus docking and infection.
In the endosome, hemagglutinins undergo conformational changes due to a pH drop to of 5–6.5 enabling viral attachment through a fusion peptide.
[10] Alfred Gottschalk proved in 1957 that hemagglutinins bind a virus to a host cell by attaching to sialic acids on carbohydrate side chains of cell-membrane glycoproteins and glycolipids.
Only when cleaved by host proteins, does each monomer polypeptide of the homotrimer transforms into a dimer – composed of HA1 and HA2 subunits attached by disulfide bridges.