title: Simulation of homology models for the extracellular domains (ECD) of ErbB3, ErbB4 and the ErbB2-ErbB3 complex in their active conformations.
abstract: Epidermal growth factor receptors (EGFR) are associated with a number of biological processes and are becoming increasingly recognized as important therapeutic targets against cancer. In this work, we provide models based on homology for the extracellular domains (ECD) of ErbB3 and ErbB4 in their active conformations, including a Heregulin ligand, followed by further refinement of the models by molecular dynamics simulations at atomistic scale. We compare the results with a model built for ErbB2 based on crystallographic information and analyze the common features observed among members of the family, namely, the periscope movement of the dimerization arm and the hinge displacement of domain IV. Finally, we refine a model for the interaction of the ECDs corresponding to a ErbB2-ErbB3 heterodimer, which is widely recognized to have a high impact in cancer development.
authors.affiliation: BIOPHYM, Macromolecular Physics Department, Instituto de Estructura de la Materia, CSIC, Serrano 113 bis, 28006, Madrid, Spain.
authors.forename: Juan Felipe
authors.initials: JF
authors.lastname: Franco-Gonzalez
authors.forename: Javier
authors.initials: J
authors.lastname: Ramos
authors.forename: Victor L
authors.initials: VL
authors.lastname: Cruz
authors.forename: Javier
authors.initials: J
authors.lastname: Martínez-Salazar
mesh_terms: D066246:ErbB Receptors / Q000737:chemistry*; D006801:Humans; D008024:Ligands; D056004:Molecular Dynamics Simulation; D020890:Neuregulin-1 / Q000737:chemistry*; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D055503:Protein Multimerization; D017433:Protein Structure, Secondary; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000737:chemistry*; D020893:Receptor, ErbB-3 / Q000737:chemistry*; D066247:Receptor, ErbB-4; D040681:Structural Homology, Protein; D014867:Water / Q000737:chemistry
chemical_list: D066246:ErbB Receptors; D008024:Ligands; D020890:Neuregulin-1; D018719:Erb-b2 Receptor Tyrosine Kinases; D020893:Receptor, ErbB-3; D066247:Receptor, ErbB-4; D014867:Water; C094131:NRG1 protein, human; C508053:ERBB2 protein, human; C581292:ERBB3 protein, human; C587689:ERBB4 protein, human