Fig. 2: The architecture of the ACE2-bound spike trimer of Omicron.

a Cryo-EM map of the one-RBD-up conformation of the Omicron spike protein in complex with hACE2 at 2.40 Å resolution. The ACE2 receptor is colored in cyan, and three protomers of the spike are colored corresponding to Fig. 1b. The inset box corresponds to the RBD-hACE2 region used for local refinement. b Density map of the Omicron RBD-hACE2 region at 3.24 Å resolution after local refinement for the boxed region in a. c Density map of the Omicron RBD-hACE2 interface with the fitted atomic model. Residues are shown as sticks, and density is represented in mesh. d–f Detailed interactions between RBD and hACE2. Yellow, red, and purple dashed lines represent hydrogen bonds, salt bridges and π-π interactions, respectively. g Superimposition of the apo and ACE2-bound spike trimers of Omicron that are reconstructed from the density maps at 3.03 Å and 2.85 Å resolution, respectively. h Conformational comparison of the interface between A_RBD and C_RBD in the apo and ACE2-bound spike trimers of Omicron. The apo spike trimer is colored in gray, and the C_RBD and A_RBD of the ACE2-bound spike trimer are colored in dark sea green and medium slate blue, respectively. The locations of residues F486 of the C_RBD, L371, P373 and F375 of the A_RBD are labeled with balls. i The relative population of RBD states observed in cryo-EM structures of ACE2-bound spikes for the prototype³⁰, Omicron and Omicron-S-L371S/P373S/F375S mutant. j Cryo-EM map of the three-RBD-up conformation of the Omicron-L371S/P373S/F375S mutant in complex with hACE2 at 3.20 Å resolution. The ACE2 receptor is colored in cyan, and three protomers of the spike trimer are colored in khaki, light pink, and sky blue, respectively. k Alignment of the RBDs from the Omicron, Omicron-3mut (Omicron-S-L371S/P373S/F375S mutant), and the prototype (PDB: 6LZG)⁴¹. The RBDs of Omicron, Omicron-3mut, and the prototype are colored in purple, yellow and gray, respectively.