Structure of a VEGF-VEGF receptor complex determined by electron microscopy.
Receptor tyrosine kinases are activated upon ligand-induced dimerization. Here we show that the monomeric extracellular domain of vascular endothelial growth factor (VEGF) receptor-2 (VEGFR-2) has a flexible structure. Binding of VEGF to membrane-distal immunoglobulin-like domains causes receptor dimerization and promotes further interaction between receptor monomers through the membrane-proximal immunoglobulin-like domain 7. By this mechanism, ligand-induced dimerization of VEGFR-2 can be communicated across the membrane, activating the intracellular tyrosine kinase domains.
Ruch
Claudia
C
Paul Scherrer Institut, Biomolecular Research, Molecular Cell Biology, CH-5232 Villigen-PSI, Switzerland.
Skiniotis
Georgios
G
Steinmetz
Michel O
MO
Walz
Thomas
T
Ballmer-Hofer
Kurt
K
D019281:Dimerization; D006801:Humans; D008024:Ligands; D008854:Microscopy, Electron; D017434:Protein Structure, Tertiary; D042461:Vascular Endothelial Growth Factor A / Q000737:chemistry* / Q000648:ultrastructure*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000737:chemistry* / Q000648:ultrastructure*
D008024:Ligands; D042461:Vascular Endothelial Growth Factor A; D040301:Vascular Endothelial Growth Factor Receptor-2