Zahra Motamedi - Department of Animal Sciences and Biotechnology, Faculty of Life Sciences and Biotechnology, Shahid Beheshti University
Maryam Azimzadeh Irani - Department of Animal Sciences and Biotechnology, Faculty of Life Sciences and Biotechnology, Shahid Beheshti University

The ErbB family has four known homologous members including EGFR, ErbB2, ErbB3 and ErbB4. EGFR, which is a key member of the ErbB glycoprotein family that triggers cellular processes and apoptosis. Its overexpression or mutation has been observed in a variety of human cancers. Ligand binding to the extracellular domain of the ErbB proteins leads to receptors activation and initiation of the signaling cascades in the cytosol. ErbB2 has a high level of constitutive activity which is not dependent to ligand binding, and its overexpression can drive tumor growth specifically in breast cancer. The members of the ErbB family could form homo and heterodimers with each other in the active form. Formation of heterodimers, increases the variety of ligands identified by these receptors and signaling pathways that can be activated by a given receptor. Furthermore, glycosylation of the ErbB proteins has shown to be important in their sorting, stability and protein–protein interactions. Here molecular Dynamics simulations of the ErbB2-EGFR were carried out for the first time and it was shown that the glycosylated heterodimer forms stronger interactions in the hydrophobic pocket located at the dimeric interface. And glycosylation occludes ErbB2 potential binding site for the growth factors.

Heterodimer, EGFR, ErbB2, Glycosylation, Molecular Dynamics Simulations