Figure 3  Binding of avian, pandemic (pdm) and seasonal HAs to specific sialyl glycans. (a) HA trimer binding to sialyl glycan receptors on the host cell surface. (b) Direct interactions in stick models between aa residues in avian/1963 (green smudge color), pdm/1968 (deep blue color) and seasonal/2007 (raspberry color) H3 HA receptor binding sites and sugar residues, a part of lactoseries tetrasaccharide a (LSTa; Neu5Acα2,3Galβ1,3GlcNAcβ1,3Galβ1,4Glc), 6′sialyl di-N-acetyllactosamine (6′SLNLN; Neu5Acα2,6(Galβ1,4GlcNAc)2) and 6′SLNLN, respectively. Neu5Ac, magenta; Gal, yellow; GlcNAc, blue. (c) Comparison of the number of glycosylation sites (green residues) on the HA1 globular head trimer (surface diagram) between avian, pdm and seasonal H3 HAs. Glycans were in silico added into N-glycosylation sites (NXS/T, X = any residue except for Pro) on the H3 HA heads by GlyProt and are shown as sticks with organic spheres. (d) Alignment showing aa changes in RBS (H3 numbering). Amino acids in avian, pdm and seasonal H3 HAs and in H17–H18 HAs generating a shallow pocket are labeled red and blue, respectively. Highly conserved amino acids giving direct interactions with Sia are highlighted in green. Well-known amino acids in HA sequences that are critical for determination of the sialyl linkage-type of avian and human host cells are highlighted in cyan. 1mqm, 6tzb, 6aov and 6bkt are from [149,150,151,152], respectively. The amino acid alignments shown in this figure and in the other figures were performed by using Clustal Omega [153].