Human betacellulin structure modeled from other members of EGF family.
We have modeled betacellulin (BTC) to gain insight into the structural elements that can explain its properties. The epidermal growth factor (EGF) signal transduction pathway, a significant mediator of several cell functions, is based on four closely related tyrosine kinase receptors. The ErbB receptors are transmembrane glycoproteins and signal transduction is initiated by ligand binding that induces receptor homo- or heterodimerization to form a complex containing two molecules of ligand and two molecules of receptor. The EGF family of ligands can be divided into three groups based on their ability to bind and activate distinct ErbB receptor homo- and heterodimers. Each member of the group formed by BTC, heparin binding EGF (HB-EGF) and epiregulin (EP) can interact with both the EGF receptor (EGFR) and heregulin receptors (ErbB-3 and ErbB-4), and are hence called "bispecific" ligands. BTC and EP also present the distinctive feature that they activate all possible heterodimeric ErbB receptors. BTC has been modeled with the program MODELLER, using human EGF, human transforming growth factor alpha (hTGFalpha), human HB-EGF and human heregulin one alpha (hHRG-1alpha) as templates. The structure of the model as well as that of the templates were optimized and a simulation of 100 ps was run for all. The main structural properties of the model and the templates were compared and in conclusion the hBTC conformation was closely similar to that of hTGFalpha.
Institut de Biotecnologia i de Biomedicina Vicent Villar Palasí and Departament de Bioquímica, Universitat Autònoma de Barcelona, Spain.
Inés
I
López-Torrejón
Enrique
E
Querol
Francesc X
FX
Avilés
Masaharu
M
Seno
Rafael
R
de Llorens
Baldomero
B
Oliva
D000595:Amino Acid Sequence; D066259:Betacellulin; D004815:Epidermal Growth Factor / Q000737:chemistry*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000737:chemistry*; D008024:Ligands; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D016211:Transforming Growth Factor alpha / Q000737:chemistry*
C587851:BTC protein, human; D066259:Betacellulin; D036341:Intercellular Signaling Peptides and Proteins; D008024:Ligands; D016211:Transforming Growth Factor alpha; D004815:Epidermal Growth Factor