Identification of individual amino acids in platelet‐derived growth factor that contribute to the specificity towards the β‐type receptor

FEBS Letters

Jaumann, Monika¹  Tatje, Dieter¹  Hoppe, Jürgen¹ 

[1] Theodor Boveri Institute (Biozentrum) der Universität Würzburg, Physiologische Chemie II, Am Hubland, W-8700 Würzburg, Germany

关键词: Growth factor;    Mutagenesis;    Receptor;    Binding site;   

DOI  :  10.1016/0014-5793(92)80456-Q

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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 α or β. Whereas PDGF-AA binds only to the α-receptor, PDGF-BB binds and activates both receptors with high affinity. To map regions that are specific for the β-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 β-receptor. In domain I the exchange of residues Pro²⁶→Arg together with Ser²⁸→Asn switched the specificity towards the β-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.

【 授权许可】

Unknown