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. 2018 Aug 16;92(17):e00547-18. doi: 10.1128/JVI.00547-18

FIG 5.

FIG 5

Receptor mimicking of 13D4 and footprint comparison of 13D4 and other H5 neutralizing antibodies. (A) Hydrogen bonding between receptor analogue LSTa and the RBS as shown in the co-crystal structure (PDB no. 3ZP0). (B) Hydrogen bonding between the 13D4 HCDR3 tip and the RBS. (C) The carbohydrate group of the LSTa SIA terminus stretches into a hydrophobic cavity enfolded by side chains of Trp153, Leu194, and Ile155. (D) V100H of HCDR3 mimics the hydrophobic interaction with the RBS, resembling the carboxylate group of the LSTa SIA terminus. (E) Overlay of the 13D4 HCDR tip with representative RBS-directed neutralizing antibodies. The Glu at the tip of 13D4 HCDR3 (green) is different from the Asps of other antibodies; the longer side chain of Glu forms four hydrogen bonds with S136 to S137, more than the hydrogen bond numbers formed by Asp at the HCDR3 tips of other antibodies: H5.3 (PDB accession no. 4XNM; orange), CH65 (3SM5; cyan), 5J8 (4M5Z; teal), HC19 (2VIR; white), HC63 (1KEN; purple), Fo45-092 (4O5I; brown), and AVFluIgG03 (5DUP; pink). (F) Sequence alignment of HCDR3 RBS-directed antibodies highlighting the Glu at the tip of 13D4 HCDR3, which is distinct from those of other antibodies. The same color scheme as in panel E was used. (G) Comparison of the binding sites of 13D4 and other H5-specific antibodies that recognize the HA1 globular head domain. The immune complex structures are overlaid in surface mode: 13D4 (green) in AVFluIg03 (PDB accession no. 5DUP; pink), H5.3 (4XNM; orange), 65C6 (5DUM; yellow), 100F4 (5DUR; pale cyan), FLD194 (5A3I; cyan), and H5M9 (4MHH; brown). (H) The view is horizontally rotated 90° with respect to panel G. (I) Footprints of three H5N1 RBS-targeting antibodies. The HA head region is shown in surface representation with the overlapping region in salmon and the unique binding residues in green, pink, and orange for 13D4, AVFluIgG03, and H5.3, respectively. (J) Footprints of four H5N1 non-RBS-directed antibodies. Table 4 details the neutralization breadths and evolving germ lines for these antibodies.