The crystal structure of placental growth factor in complex with domain 2 of vascular endothelial growth factor receptor-1.
Placental growth factor (PlGF) is a member of the vascular endothelial growth factor (VEGF) family and plays an important role in pathological angiogenic events. PlGF exerts its biological activities through binding to VEGFR1, a receptor tyrosine kinase that consists of seven immunoglobulin-like domains in its extracellular portion. Here we report the crystal structure of PlGF bound to the second immunoglobulin-like domain of VEGFR1 at 2.5 A resolution and compare the complex to the closely related structure of VEGF bound to the same receptor domain. The two growth factors, PlGF and VEGF, share a sequence identity of approximately 50%. Despite this moderate sequence conservation, they bind to the same binding interface of VEGFR1 in a very similar fashion, suggesting that both growth factors could induce very similar if not identical signaling events.
Christinger
Hans W
HW
Department of Protein Engineering Genentech, Inc., South San Francisco, California 94080, USA.
Fuh
Germaine
G
de Vos
Abraham M
AM
Wiesmann
Christian
C
D000595:Amino Acid Sequence; D002942:Circular Dichroism; D018360:Crystallography, X-Ray; D006801:Humans; D020128:Inhibitory Concentration 50; D008024:Ligands; D008954:Models, Biological; D008958:Models, Molecular; D008969:Molecular Sequence Data; D000072483:Placenta Growth Factor; D011257:Pregnancy Proteins / Q000737:chemistry*; D011485:Protein Binding; D017510:Protein Folding; D020033:Protein Isoforms; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000737:chemistry* / Q000378:metabolism
D008024:Ligands; C000608036:PGF protein, human; D011257:Pregnancy Proteins; D020033:Protein Isoforms; D000072483:Placenta Growth Factor; D040281:Vascular Endothelial Growth Factor Receptor-1