Fig. 3: Structure of anti-NA mAbs targeting the SA-binding site.
From: A pan-influenza antibody inhibiting neuraminidase via receptor mimicry
a, Topology of the complex formed by FNI9 (light blue) binding to NA (grey). Representative calcium ions at the centre of the tetramer and in the NA–Fab interface are represented as red spheres. Glycans decorating each NA protomer are shown in green (see Extended Data Fig. 7). b, Binding of FNI9 (light blue), FNI17 (dark blue) and FNI19 (light green) to the NA (grey) SA-binding pocket. Only the variable domains of the mAbs are shown. VH, variable domain heavy chain; VK, variable domain kappa light chain. c, Network of salt bridges and hydrogen bond interactions between R106 and D107 (light blue sticks) in the HCDR3 of FNI9 and R118, D151, E227, R292 and R371 in NA (grey sticks). The dashed lines depict interactions within 3.5 Å. d, Network of salt bridges and hydrogen bonds between SA (orange) and NA-binding pocket residues (grey) based on PDB: 4GZQ. The dashed lines are depicted as in c. e, Network of salt bridges and hydrogen bonds between oseltamivir (OSE; pink) and NA-binding pocket residues (grey) based on PDB: 4GZP. The dashed lines are depicted as in c. f, Hydrogen bonds between residues T107, R108 and G109 (green) in the HCDR3 of 1G01 (PDB: 6Q23) and the NA-binding pocket residues (grey). The dashed lines are depicted as in c. g, Overlay of SA, OSE and the HCDR3 of FNI9 illustrates the molecular mimicry of their carboxylates participating in a tridentate salt bridge with R118, R292 and R371. The dashed lines are depicted as in c. h,i, Logo plot amino acid conservation of SA, OSE, FNI9, FNI17, FNI19 and 1G01 epitopes based on available NA sequences from human seasonal H1N1 (n = 64,476) and H3N2 (n = 91,754) IAVs (h) and Victoria/2/87-like (n = 23,787) and Yamagata/16/88-like (n = 17,769) IBVs (i). Key contact residues are shown in red. The binding energies of epitope residues (as a percentage of the total) are shown in the heat map; for the IBV analyses, PDB 1NSC (SA, B/Beijing/1/87) and 4CPY (OSE, B/Lyon/CHU/15.216/2011) were used.
