Fig. 4: Structure basis of the interaction between H2N2 HAs and avian and human receptor analogs.

The secondary structural elements of the RBS (130-loop, 140-loop, 190-helix, and 220-loop; H3 number) are labeled in the ribbon representation, together with selected residues in the stick representation. Hydrogen bonds are indicated by the dashed lines. a, b Molecular interactions of Dk/FJ/2021 wild-type HA with human (a) and avian (b) receptor analogs. c Comparison of the RBSs between the Dk/FJ/2021 HA-avian receptor complex (light pink) and the Dk/FJ/2021-S144N HA mutant-avian receptor complex (orange). A similar trans conformation for glycan binding showed no observable drift between the two complexes. d, e Molecular interactions of A/SG/1/1957 HA with human (d) and avian (e) receptor analogs. f Comparison of the RBSs between the A/SG/1/1957 HA-human receptor complex (cyan) and A/SG/1/1957-R137M HA mutant-human receptor complex (lavender). The human receptor analog shifts towards the 130-loop by 0.8 Å in the A/SG/1/1957-R137M complex. g Comparison of the RBSs between the A/SG/1/1957 HA-human receptor complex (cyan) and A/SG/1/1957-N144E HA mutant-human receptor complex (green). The human receptor analog shifts towards the 220-loop by 1.3 Å in the A/SG/1/1957-N144E complex. h Comparison of the RBSs between the A/SG/1/1957 HA-human receptor complex (cyan) and A/KR/426/1968 HA-human receptor complex (pale green). The human receptor analog shifts towards the 130-loop by 0.8 Å in the A/KR/426/1968 complex.