Fig. 5: Structural analysis of TAU-2212 in complex with the SARS-CoV-2 spike trimer.

a Ribbon diagram showing the crystal structure of Fab2212. The heavy and light chains are colored pink and light green, respectively. The CDR loops are colored yellow. The missing residues 141–151 and 197–204 of the heavy chain are shown as pink dashed lines. b Surface diagrams showing the side (left) and the top open-up (right) views of the spike trimer with three bound Fabs of mAb TAU-2212. The RBDs of the spike trimer are colored blue and the Fab2212 heavy and light chains are colored as in a. The binding epitopes of the heavy and light chains around the junction of two RBDs are colored yellow and white, respectively. Residue E484 is indicated in red. c Surface (top) and ribbon (bottom) diagrams showing the five conformations of the TAU-2212-spike complex. The heavy and light chains of the bound mAbs are colored are colored as in a. The spike trimers are in gray. The number pairs X, X' indicate Fabs from the same mAb. d Detailed interactions between TAU-2212 and the spike trimer, illustrated with the high-resolution conformation 1 structure. Heavy chain and light chain CDR loops involved in direct interactions are shown in pink and cyan, respectively. Residues involved in hydrogen bond formation are shown in sticks with oxygen and nitrogen atoms colored red and blue, respectively. e Ribbon and stick diagrams showing the disruption of the key hydrogen bonds in E484 by the E484K mutation. f Surface diagrams showing mapping of key mutations in different variants and the positions of the mutated sites relative to the binding epitopes recognized by TAU-2212. The TAU-2212 heavy and light chain epitopes are colored yellow and white, respectively. The mutation sites within or outside the binding epitope of TAU-2212 are colored red and green, respectively. g Structural comparisons of the Fabs in conformations 1, 4, and 5. The alignments were performed by using the RBDs (in gray) and the variable regions of the bound Fabs. The bound Fabs of conformations 1, 4, and 5 are colored orange, black, and blue, respectively.