Human betacellulin structure modeled from other members of EGF family |
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Authors: | López-Torrejón Inés Querol Enrique Avilés Francesc X Seno Masaharu de Llorens Rafael Oliva Baldomero |
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Institution: | (1) Institut de Biotecnologia i de Biomedicina Vicent Villar Palasí and Departament de Bioquímica, Universitat Autònoma de Barcelona, 08193 Bellaterra, Barcelona, Spain E-mail: boliva@imim.es Phone: +34 93 5422933 Fax: +34 93 5422802, ES;(2) Department of Bioscience and Biotechnology, Faculty of Engineering, Graduate School of Natural Science and Technology, Okayama University, 3-1-1 Tsushima-Naka, Okayama 700-8530, Japan, JP;(3) Departament de Biologia, Facultat de Ciències, Universitat de Girona, 17071 Girona, Spain, ES;(4) Laboratori de Biologia Estructural Computacional, Grup de Recerca d Informàtica Biomèdica, Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, C/ Doctor Aiguader, 80, 08003 Barcelona, Spain, ES |
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Abstract: | 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 (hTGF ), human HB-EGF and human heregulin one alpha (hHRG-1 ) 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 hTGF . Electronic supplementary material to this paper can be obtained by using the Springer LINK server located at http://dx.doi.org/10.1007/s00894-002-0072-2.Electronic Supplementary Material available. |
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Keywords: | Betacellulin – Epidermal growth factors – ErbB receptors |
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