Research objectives and content
The Epidermal growth factor receptor (EGF-R) is a prototype tyrosine kinase receptor widely expressed in mammalian epitelial tissues, and it has been found to be overexpressed in many tumours of epitelial origin, being a potential target for antitumour therapy. In spite of its functional importance, the three-dimensional structure of the EGF-R is presently unknown. Its determination is of both theoretical and practical interest, since it could lead to the development of new drugs targeting the receptor. The main objective of this project is to obtain the 3D structures of EGF-R and its complexes with EGF and Tgf-alpha by crystallography. The deglycosylated external region will be crystallized alone and in complex with EGF and TGF-alpha. The X-ray diffraction pattern of the crystals will be obtained and analyzed in order to determine the 3D structure of the external region and the complexes. Our approach is innovative in three important aspects It aims to obtain a homogeneous EGF-R external region by using a recombinant deglycosylated polypeptide; it considers the possibility of crystallyzing each domain separately and it constitutes the first attempt to crystallize the EGF-R together with TGF-alpha. This will allow us to determine the ligandreceptor interactions, opening the way to the design of EGF antagonists.