Fig. 3: Cryo-EM structure of the Omicron spike-S309 complex.

a Cryo-EM map of the one-RBD-up conformation of the Omicron spike protein in complex with three S309 Fabs at 2.50 Å resolution. Three protomers of the spike are colored corresponding to Fig. 1b. The heavy and light chains of the S309 Fab are colored in hot pink and forest green. The inset box corresponds to the RBD-S309 region used for local refinement. b Cryo-EM map of the RBD-S309 region at 2.80 Å resolution after local refinement for the boxed region in a. c Density map of the Omicron RBD-S309 interface with the fitted atomic model. Residues are shown as sticks, and density is represented in mesh. d Detailed interactions between Omicron RBD (orange) and S309 Fab (hot pink and forest green). The N-linked glycan of N343 in the RBD is colored in purple. Yellow and red dashed lines represent hydrogen bonds and salt bridges, respectively. e Comparison of key residues of the epitope targeted by S309 in the prototype (yellow) (PDB: 6WPT)⁶ and Omicron (orange). Key residues shared by the prototype and Omicron are labeled in purple, otherwise are labeled with their respective colors. Mutations of the Omicron RBD are shown as spheres. N-linked glycan of the residue N343 in the prototype or Omicron is colored in cyan or purple. f The structure of the S309-RBD-RBD-S309 region at 2.66 Å resolution after local refinement (left panel). The colors shown correspond to a. The interfaces between up-RBD (A_RBD) and down-RBD (C_RBD) in the apo and S309-bound Omicron spikes were compared (right panel). The locations of residues F486 of the C_RBD, L371, P373, and F375 of the A_RBD are labeled with balls.