Fig. 1: Structural evolution of human H3N2 HA RBS.

a, b Structures of HK68 HA in complex with 6′SLNLN (gray, PDB 6TZB)²⁹, Ecu16 HA in complex with 6′SLNLN (green, PDB 8TJA)², and Vic20 HA in complex with LSTc (blue, PDB 8FAW from this study) are aligned based on the receptor-binding subdomain (HA1 residues 117-265)³⁶. a Front and b side views are shown. Representative differences in receptor conformations are indicated by the curved arrow. c Interactions between HK68 HA and 6′SLNLN are shown. d Interactions between Ecu16 HA and 6′SLNLN are shown. e Interactions between Vic20 HA and LSTc are shown. Hydrogen bonds are represented by black dashed lines. Water molecules are shown as red spheres. Human-type receptor analogs (6′SLNLN and LSTc) are shown as yellow sticks. f The height of the RBS in HA apo form is measured by the distances between the Cα of residues 186 (Cα₁₈₆) and the Cα of residues 228 (Cα₂₂₈), as well as between the Cα of residues 190 (Cα₁₉₀) and the phenolic oxygen of residue 98 (OH₉₈). g Distances of Cα₁₉₀–OH₉₈ and Cα₁₈₆–Cα₂₂₈ in different human H3N2 HAs were measured. HK68: PDB 4FNK⁵⁹, Bris07: PDB 6AOQ²⁴, Fin04: PDB 2YP2⁸, HK05: PDB 2YP7⁸, Vic11: PDB 4O5N⁶⁰, Mich14: PDB 6BKP¹¹, Vic20 is from this study (PDB 8FAQ). Amino acid sequences at residues 186 and 190 on HA of different strains are shown. f, g Of note, the HA apo structure of Ecu16 was not available, and thus not included in this analysis. Raw data are provided as a Source Data file.