Fig. 2: Structural basis of the enhanced Omicron S–ACE2 interaction.
From: Molecular basis of receptor binding and antibody neutralization of Omicron
a, Measurement of the binding affinity between the ACE2 monomer and the S trimer of the G614 (left), Delta (middle) and Omicron (right) variants using biolayer interferometry. Biotinylated S trimers were loaded onto streptavidin sensors and were then allowed to interact with different concentrations of ACE2 (shown on the right). Raw sensorgrams and fitting curves are shown in colour and grey, respectively. Association and dissociation phases are divided by the red dashed lines. Kdis, dissociation rate; Kon, ‘on-rate’. b, Cryo-EM maps of the Omicron S–ACE2 complex in three distinct conformational states. In the S–ACE2-C2 and S–ACE2-C3 maps, the density of RBD-2-associated or RBD-3-associated ACE2 appears weaker than that of the stably associated ACE2 on RBD-1 (see also Extended Data Fig. 3c). ACE2 is shown in violet red. This colour scheme is followed throughout. c, Density map of the focus-refined Omicron RBD-1–ACE2 and the zoomed-in view of the RBD–ACE2 interaction interface, showing the side chain densities of Q493R, G496S, Q498R, N501Y and Y505H on the RBM. d, The substituted residues R493, S496, R498 and H505 of the Omicron RBM form new interactions with E35, D38, Q42 and K353 of ACE2 (the spring represents the salt bridge, and the black dashed line represents the hydrogen bond) relative to that in the WT RBD–ACE2 (PDB: 6M0J; dark grey). A newly formed hydrogen bond without substitution is shown by a red dashed line. e, Interaction interface areas between ACE2 and the RBD of Omicron, Delta (PDB: 7W9I) and WT (PDB: 6M0J), analysed using PISA. f, The electrostatic surface properties of Omicron, Delta (PDB: 7W9I) and WT (PDB: 6M0J) RBDs, with the mutated residues indicated. The black outlines depict the footprint of ACE2 on the RBD. g, The electrostatic surface property of ACE2, with residues in proximity to RBD-1 (less than 4 Å) indicated (related to Extended Data Table 3).
