Markovic-Mueller S Stuttfeld E Asthana M Weinert T Bliven S Goldie KN Kisko K Capitani G Ballmer-Hofer K 2017 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 of VEGFR/VEGF complexes based on single-particle electron microscopy, small-angle X-ray scattering, and X-ray crystallography revealed the location of VEGF binding and domain arrangement of individual receptor subdomains. Here, we describe the structure of the full-length VEGFR-1 extracellular domain in complex with VEGF-A at 4 Å resolution. We combined X-ray crystallography, single-particle electron microscopy, and molecular modeling for structure determination and validation. The structure reveals the molecular details of ligand-induced receptor dimerization, in particular of homotypic receptor interactions in immunoglobulin homology domains 4, 5, and 7. Functional analyses of ligand binding and receptor activation confirm the relevance of these homotypic contacts and identify them as potential therapeutic sites to allosterically inhibit VEGFR-1 activity. application/pdf https://sonar.ch/global/documents/202374 eng info:eu-repo/semantics/altIdentifier/doi/10.1016/j.str.2016.12.012 info:eu-repo/semantics/altIdentifier/pmid/28111021 info:eu-repo/semantics/openAccess Structure (London, England : 1993). - 2017 VEGF receptor X-ray crystallography angiogenesis extracellular domain receptor tyrosine kinase single-particle negative stain electron microscopy small-angle X-ray scattering vascular endothelial growth factor Amino Acid Sequence Binding Sites Cloning, Molecular Crystallography, X-Ray Gene Expression Humans Ligands Microscopy, Electron Models, Molecular Protein Binding Protein Conformation, alpha-Helical Protein Conformation, beta-Strand Protein Interaction Domains and Motifs Protein Multimerization Recombinant Proteins Sequence Alignment Sequence Homology, Amino Acid Thermodynamics Vascular Endothelial Growth Factor A Vascular Endothelial Growth Factor Receptor-1 Structure of the Full-length VEGFR-1 Extracellular Domain in Complex with VEGF-A. http://purl.org/coar/resource_type/c_6501