The Structural Basis for the Specificity of Epidermal Growth Factor and Heregulin Binding

• Published in: The Journal of biological chemistry 1995-04, Vol.270 (16), p.9585-9589
• Main Authors: Barbacci, E G, Guarino, B C, Stroh, J G, Singleton, D H, Rosnack, K J, Moyer, J D, Andrews, G C
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Carrier Proteins - chemistry; Carrier Proteins - metabolism; Epidermal Growth Factor - chemistry; Epidermal Growth Factor - metabolism; ErbB Receptors - metabolism; Glycoproteins - chemistry; Glycoproteins - metabolism; Humans; Molecular Sequence Data; Neuregulin-1; Peptide Fragments - metabolism; Proto-Oncogene Proteins - metabolism; Receptor, ErbB-3; Sensitivity and Specificity; Structure-Activity Relationship
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.270.16.9585

Heregulin is a ligand for the erb B3 and erb B4 receptors, with a region of high homology to epidermal growth factor (EGF). Despite this homology, these ligands bind to their corresponding receptors with great specificity. We report here the synthesis of heregulin β 177-241 and show that a region consisting of amino acids 177-226 is sufficient both for binding and stimulation of receptor phosphorylation. Studies of chimeric EGF/heregulin peptides revealed that amino acids 177-181 of heregulin provide the specificity for binding to the heregulin receptor. The substitution of amino acids 177-181 of heregulin for the N terminus of EGF produced a unique bifunctional agonist that binds with high affinity to both the EGF receptor and the heregulin receptor.