Crystal structure of human VEGF-D and its comparison to the other VEGF family ligands. (A). A cartoon representation of the crystal structure of the covalent VEGF-D (Cys117Ala mutant) homodimer in magenta and pink. The N-terminal residues between the 2 reported proteolytic cleavage sites are colored in yellow.¹⁷  The sugar moieties and the disulfide bonds are shown in gray and yellow sticks, respectively. N- and C-termini, the N-terminal helix (αN), and the connecting loops 1-3 (L1-L3) are labeled where applicable. (B). Close-up of the N-terminal helix (αN) in the same orientation as in panel A. The helix is shown in a cartoon loop representation with the same coloring as in panel A. Asp103 and Trp106, the equivalents of the VEGFR-2 binding VEGF-C residues Asp123 and Trp126,¹⁸  and the first α-helical residues Thr92-Lys100 are shown as sticks. (C) Superposition of the VEGF-D (magenta and yellow) and VEGF-A (PDB code 1FLT; green) monomer structures with VEGF-C (PDB code 2X1W; orange) in the VEGFR-2 complex structure. The C_α-traces are shown as ribbon diagrams. Labeling is as in panel A, except that the N-termini are labeled according to the VEGF coloring in the figure. (D) The VEGF-D and VEGF-A monomer structures from panel C are superimposed with VEGF-C in the VEGF-C/VEGFR-2D23 complex structure. For clarity, VEGF-C is not shown. VEGFR-2 D2 (R2-D2) and D3 (R2-D3) are shown as a molecular surface model in gray. Coloring as indicated in panel C.