Structure of the Full-length VEGFR-1 Extracellular Domain in Complex with VEGF-A

摘要: Vascular endothelial growth factors (VEGFs) regulate blood and lymph vessel development upon activation of three receptor tyrosine kinases: VEGFR-1, -2, and -3. Partial structures VEGFR/VEGF complexes based on single-particle electron microscopy, small-angle X-ray scattering, crystallography revealed the location VEGF binding domain arrangement individual subdomains. Here, we describe structure full-length VEGFR-1 extracellular in complex with VEGF-A at 4 A resolution. We combined crystallography, molecular modeling for determination validation. The reveals details ligand-induced dimerization, particular homotypic interactions immunoglobulin homology domains 4, 5, 7. Functional analyses ligand confirm relevance these contacts identify them as potential therapeutic sites to allosterically inhibit activity.