Binding interfaces between the aminoterminal helices (αN) and loops L1-L3 of the VEGFs and VEGFR-2 D2 and D3, representing the major ligand-binding domain. Key residues are highlighted and labeled using VEGFR-2 and VEGF-A numbering, except for Asn89 of VEGF-E. VEGF-A is shown in red, VEGF-C is shown in green, VEGF-E is shown in blue, and VEGFR-2 D23 is shown in gray. Hydrogen bonds and salt bridges are shown by gray dashed lines. In panel A, the view is centered on the aminoterminal helices (αN) of VEGFs, and in panel B, on the contacts between L2 of VEGF with D3 of the receptor. (C) Interaction of loop L3 of VEGFs with VEGFR-2 D23. Hydrogen bonds and hydrophobic interactions for VEGF-A His86 and VEGF-E Asn89 are shown by gray dashed lines. (D) The binding interfaces between loops L1 and L3 of the VEGFs with VEGFR-2.