Solution structure of betacellulin, a new member of EGF-family ligands

• Published in: Biochemical and biophysical research communications 2002-06, Vol.294 (5), p.1040-1046
• Main Authors: Miura, Kazunori, Doura, Hideki, Aizawa, Tomoyasu, Tada, Hiroko, Seno, Masaharu, Yamada, Hidenori, Kawano, Keiichi
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Betacellulin; Epidermal Growth Factor - chemistry; Epidermal growth factor family; Growth Substances - chemistry; Humans; Intercellular Signaling Peptides and Proteins; Ligands; Mice; Models, Molecular; Molecular Sequence Data; Nuclear magnetic resonance; Nuclear Magnetic Resonance, Biomolecular; Protein Structure, Tertiary; Solution structure; Static Electricity
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/S0006-291X(02)00585-5

The solution structure of the EGF-like domain of betacellulin (BTCe), a newly discovered member of the epidermal growth factor (EGF) family, has been determined using two-dimensional nuclear magnetic resonance spectroscopy. This is the first report to identify the solution structure of the EGF-family ligand monomers that interact with both ErbB-1 and ErbB-4. The solution structure of BTCe was calculated using 538 NMR-derived restraints. The overall structure of BTCe was stabilized by three disulfide bonds, a hydrophobic core, and 23 hydrogen bonds. It appears that BTCe is comprised of five β-strands and one short 3 10 helical turn. The secondary structural elements of BTCe are basically similar to those of the other EGF-family proteins, except that several significant variations of the structural properties were found. It is suggested that the structural variations between BTCe and the other EGF-family ligands may affect the specific receptor-recognition properties of EGF-family ligands.