Computer modelling of the receptor-binding domains of VEGF and PIGF.
Models of the platelet-derived growth factor (PDGF)-like domains of vascular endothelial growth factor (VEGF) and placenta growth factor (PIGF) were built based on their homology to PDGF. These domains contain most of the determinants for receptor binding. The sequences of these proteins exhibit limited but significant homology to that of platelet-derived growth factor (PDGF), a member of the cystine knot growth factor family. The eight cysteine residues that are involved in intra- and interchain disulphide bonds are conserved. Two high affinity receptors for VEGF have been identified, only one of which binds PIGF. The models presented here are consistent with results that show that VEGF receptor binding is mediated by charged residues in the loops. A comparison of the models suggests that the difference in receptor-binding specificity between VEGF and PIGF may be due to differences in the distribution of positively charged residues and the exposure of hydrophobic residues in the loops.
Walsh
T P
TP
Department of Biochemistry, University College, Belfield, Dublin, Republic of Ireland.
Grant
G H
GH
D000595:Amino Acid Sequence; D000818:Animals; D000925:Anticoagulants / Q000737:chemistry; D000077214:Becaplermin; D001665:Binding Sites; D002417:Cattle; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D019281:Dimerization; D016228:Endothelial Growth Factors / Q000378:metabolism*; D006801:Humans; D008222:Lymphokines / Q000378:metabolism*; D051379:Mice; D008956:Models, Chemical; D008958:Models, Molecular; D008969:Molecular Sequence Data; D000072483:Placenta Growth Factor; D010982:Platelet-Derived Growth Factor / Q000737:chemistry; D011257:Pregnancy Proteins / Q000378:metabolism*; D011487:Protein Conformation; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D020574:Proto-Oncogene Proteins c-sis; D051381:Rats; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D017978:Receptors, Growth Factor / Q000378:metabolism*; D040262:Receptors, Vascular Endothelial Growth Factor; D016415:Sequence Alignment; D012984:Software; D042461:Vascular Endothelial Growth Factor A; D040281:Vascular Endothelial Growth Factor Receptor-1; D042442:Vascular Endothelial Growth Factors
D000925:Anticoagulants; D016228:Endothelial Growth Factors; D008222:Lymphokines; C000608036:PGF protein, human; C000608037:Pgf protein, mouse; C000608038:Pgf protein, rat; D010982:Platelet-Derived Growth Factor; D011257:Pregnancy Proteins; D011518:Proto-Oncogene Proteins; D020574:Proto-Oncogene Proteins c-sis; D017978:Receptors, Growth Factor; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D000072483:Placenta Growth Factor; D000077214:Becaplermin; D020794:Receptor Protein-Tyrosine Kinases; D040262:Receptors, Vascular Endothelial Growth Factor; D040281:Vascular Endothelial Growth Factor Receptor-1