Identification of three amino acid residues in the B-chain of platelet-derived growth factor with different importance for binding to PDGF alpha- and beta-receptors.
The B-chain homodimer isoform of platelet-derived growth factor (PDGF) binds with high affinity both to alpha- and to beta-receptors. In order to localize amino acid residues in PDGF-BB of differential importance for the binding to the two receptors, PDGF-BB mutants were analyzed in which single amino acid residues were changed to alanine residues. We found that Phe-118 in loop 1 of the PDGF B-chain is crucial for binding to both receptors, and that the surrounding amino acids, Asn-117 and Leu-119, appear to be important primarily for binding to the beta-receptor. In contrast, Lys-161 in loop 3 was found to be more important for binding to alpha-receptors than beta-receptors. Previous studies have shown that the receptor binding epitope of PDGF-BB is composed mainly of loops 1 and 3; the findings of the present study show that the alpha- and beta-receptors interact with different amino acid residues in these regions.
Kreysing
J
J
Ludwig Institute for Cancer Research, Biomedical Center, Uppsala, Sweden.
Ostman
A
A
van de Poll
M
M
Bäckström
G
G
Heldin
C H
CH
D000595:Amino Acid Sequence; D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D002460:Cell Line; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed / Q000235:genetics; D009154:Mutation; D010982:Platelet-Derived Growth Factor / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D020796:Receptor, Platelet-Derived Growth Factor alpha; D020797:Receptor, Platelet-Derived Growth Factor beta; D017479:Receptors, Platelet-Derived Growth Factor / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism
D000596:Amino Acids; D010982:Platelet-Derived Growth Factor; D011994:Recombinant Proteins; D020796:Receptor, Platelet-Derived Growth Factor alpha; D020797:Receptor, Platelet-Derived Growth Factor beta; D017479:Receptors, Platelet-Derived Growth Factor