Members of the epidermal growth factor receptor family play important roles in various cellular processes, both in physiological and in pathological conditions. Dimerization and autophosphorylation of these receptor tyrosine kinases are key events of signal transduction. Details of the molecular events of the signaling are not entirely known. To facilitate the understanding of receptor structure and function at molecular level, a molecular model was built for the nearly full length ErbB2 dimer. Modeling was based on the X-ray or NMR structures of extracellular, transmembrane and intracellular domains. The extracellular domain was positioned above the cell membrane based on the distance determined by experimentally measured fluorescence resonance energy transfer. Favorable dimerization interactions are predicted for the extracellular, transmembrane and the protein kinase domains in the model of nearly full-length dimer of ErbB2, which may act in a coordinated fashion in ErbB2 homodimerization, or alternatively in ErbB heterodimerizations.

Key Words: ErbB2, FRET, epidermal growth factor receptor, molecular modeling, tyrosine kinase receptor