FIGURE 5.
X-ray crystal structure of the VEGF·dAb complexes and proposed structure of VEGF/VEGF dual dAb complex. VEGF/Vκ·dAb complex (A) and VEGF/VH·dAb complex (B) structures are depicted as secondary structure schematics with Vκ·dAbs colored in gold, VH·dAbs colored in red, and the VEGF homodimer colored in purple. In A and B, side chains of VEGF epitope and dAb paratope residues are depicted as spheres and sticks, respectively. C, in silico built model showing how a dual-dAb molecule could engage VEGF. Modeling was based on the crystal structures of the VEGF-dAb complexes. Fc homodimer and linker regions are colored gray. Fc-fused VH and Vκ·dAb regions are in red and gold, respectively (VH = VH·dAb; Vk = Vκ·dAb; Fc = hIgG Fc domain; L = peptide linker).