Fig. 4: Structural analysis of Fab2303 in complex with the SARS-CoV-2 spike trimer and RBD.

a Ribbon diagrams showing the cryoEM structure of the SARS-CoV-2 spike trimer in complex with one TAU-2303 Fab (Fab2303). The “up” RBD protomer of the spike is colored blue. The other two protomers are colored salmon. The heavy chain of Fab2303 is colored pink and the light chain is colored cyan. b Left: ribbon diagrams showing the Fab2303-RBD crystal structure superimposed onto the ACE2-RBD crystal structure (PDB: 6M0J). The RBD and Fab2303 are colored as in a. ACE2 is colored green. The solid and dashed lines in red indicate the long axes of ACE2 and Fab2303, respectively. Right: the paratope and epitope of Fab2303 shown as rendered surface representations. The paratope on Fab2303 and epitope on RBD are colored yellow. Red lines indicate the footprint of ACE2. c Detailed interactions between Fab2303 and SARS-CoV-2 RBD. HCDR and LCDR stand for complementarity-determining region (CDR) of the heavy and the light chain, respectively. LFR stands for framework region of the light chain. d Structural comparisons of RBD with RBD mutants K417N, K417T, N501Y, and E484K. Structures of the mutants were modeled in COOT⁵³ by using the single mutate function, in which only the side chains of the mutated residues were changed. Most possible side chain conformations of the mutated residues were generated and selected from the rotamer library of COOT and according to the binding energy calculated with PISA. The heavy chain of Fab2303 is colored pink and the light chain is colored cyan. The RBD and Fab2303 are colored as in a, with the mutated RBD residues in green. e Surface mapping of key mutations in different variants and the positions of the mutated sites relative to the binding epitopes recognized by TAU-2303. The binding epitopes of TAU-2303 are colored yellow. The mutation sites within or outside the binding epitope of TAU-2303 are colored red and green, respectively.