Mapping of the antigenic determinants recognized by S2-4D, S2-5D, S2-8D, and S2-4A on the prefusion and postfusion structures of the trimeric S protein and S2 subunit. (A) The antigenic determinants (E1144, F1148, L1152, F1156) of mAbs S2-4D, S2-5D, S2-8D, and S2-4A were mapped on the prefusion structure of the trimeric full-length S protein (PDB code: 6xr8). The carboxyl side chain groups of E1144 are pointed outwards, and residues F1148, L1152, and F1156 are buried inside a triple-helical structure and form a hydrophobic core. (B) The binding epitopes of mAbs S2-10H and S2-8A are marked in light gray spheres and dark gray spheres, respectively. Residues E1144 (deep blue), F1148 (blue), L1152 (marine blue), and F1156 (cyan) are located at the peripheral part of a six-helix bundle on the stalk-like structure of the S2 subunit (PDB code: 6xra). The residue E1144 of Subunit A (light blue) interacts with the residue Q762 (green) of the adjacent Subunit C (light green), and F1148, L1152, and F1156 of Subunit A interacts with the residues A989 (yellow), Q992 (magenta), I993 (red), and L996 (orange) of another adjacent Subunit B (pink).