title: Identification of individual amino acids in platelet-derived growth factor that contribute to the specificity towards the beta-type receptor.
abstract: Platelet-derived growth factor constitutes a family of three isoforms (PDGF-AA, -AB, and -BB) composed of two homologous polypeptide chains (A and B). These isoforms interact with two types of receptors termed alpha or beta. Whereas PDGF-AA binds only to the alpha-receptor, PDGF-BB binds and activates both receptors with high affinity. To map regions that are specific for the beta-receptor, we introduced mutations into PDGF-AA located in previously identified epitopes [1991, Biochemistry 30, 3303-3309]. A single amino acid exchange in domain II of PDGF-AA (Ala67----Arg) was sufficient to bring about a reduced but significant activation of the beta-receptor. In domain I the exchange of residues Pro26----Arg together with Ser28----Asn switched the specificity towards the beta-receptor. These data indicate that parts of the exposed domains are indeed involved in receptor binding. Since these single mutations lead to mutant proteins which are about 100-fold less active than PDGF-BB, it is suggested that other amino acid residues also participate in the binding to the receptors.
authors.affiliation: Theodor Boveri Institut (Biozentrum), Universität Würzburg, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Jaumann
authors.forename: D
authors.initials: D
authors.lastname: Tatje
authors.forename: J
authors.initials: J
authors.lastname: Hoppe
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D002942:Circular Dichroism; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009994:Osmolar Concentration; D010982:Platelet-Derived Growth Factor / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011487:Protein Conformation; D011956:Receptors, Cell Surface; D017479:Receptors, Platelet-Derived Growth Factor; D013329:Structure-Activity Relationship
chemical_list: D046911:Macromolecular Substances; D010982:Platelet-Derived Growth Factor; D011956:Receptors, Cell Surface; D017479:Receptors, Platelet-Derived Growth Factor