Figure 3.
Structure models of cytotoxic fusion proteins. The structure models were generated based on available structure data of domains or entities. Structural data from the Protein DataBank (PDB, Nov. 2011) (134) were assembled and minimized using DiscoveryStudio31 (135). Ribbon representations are shown to facilitate identification of secondary structures where the N-terminal domain is placed on the top and the C terminal domain on the bottom. The color scheme of the models follows that of Figure 1 and 2. A: Model of the of fibroblast growth factor receptor 1 (FGFR1) Trap composed of several different structures starting with the nuclear magnetic resonance (NMR) structure of domain 1 (pdbcode: 2CKN), a model of the acidic box based on the homology to part of coagulation factor VII, in orange (pdcode: 3CDZ), followed by domains 2 and 3, in blue (pdcode: 3OJV), and, at the C-terminal end, the Fc portion, in grey (pdbcode: 1HZH). B: The HER Trap model is composed of the extracellular domain (ECD) domain of epidermal growth factor receptor (EGFR), in blue (pdbcode: 3NJP) and the ECD domain of HER3, in green (pdbcode: 1M6B), fused to the Fc portion, in grey (pdbcode: 1HZH). C: Double antiangiogenic protein (DAAP) model is based on the first two immunoglobulin domains and the three EGF domains of tyrosine kinase receptor in endothelial cells 2 (TIE2), in green (pdbcode: 2GY7), domain-2 of vascular endothelial growth factor receptor-1 (VEGFR1), in blue (pdbcode: 2XAC), and the Fc portion, in grey (pdbcode: 1HZH). D: Model of VEGF Trap (Aflibercept) is based on the crystal structure of VEGFR1 domain-2, in dark blue (pdbcode: 1QSZ), followed by domain-3 of VEGFR2, in light blue (pdcode: 2X1W), and fused to the IgG1 Fc portion, in grey (pdbcode: 1HZH). E: A major histocompatibility complex (MHC) complex structure comprising the α chain of the MHC allele 201, in yellow, the common β2-microglobulin domain, in green, and a peptide in the groove, in magenta (pdbcode: 2VLR), is used to build the model of a fusion with on scFv, in light and dark blue; the linkers comprising G4S motifs are indicated in red.