title: Dimer-based model for heptaspanning membrane receptors.
abstract: The existence of intramembrane receptor-receptor interactions for heptaspanning membrane receptors is now fully accepted, but a model considering dimers as the basic unit that binds to two ligand molecules is lacking. Here, we propose a two-state-dimer model in which the ligand-induced conformational changes from one component of the dimer are communicated to the other. Our model predicts cooperativity in binding, which is relevant because the other current models fail to address this phenomenon satisfactorily. Our two-state-dimer model also predicts the variety of responses elicited by full or partial agonists, neutral antagonists and inverse agonists. This model can aid our understanding of the operation of heptaspanning receptors and receptor channels, and, potentially, be important for improving the treatment of cardiovascular, neurological and neuropsychyatric diseases.
authors.affiliation: Department Bioquímica i Biologia Molecular, Universitat de Barcelona, A. Diagonal, 645. 08028 Barcelona, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Franco
authors.forename: Vicent
authors.initials: V
authors.lastname: Casadó
authors.forename: Josefa
authors.initials: J
authors.lastname: Mallol
authors.forename: Sergi
authors.initials: S
authors.lastname: Ferré
authors.forename: Kjell
authors.initials: K
authors.lastname: Fuxe
authors.forename: Antonio
authors.initials: A
authors.lastname: Cortés
authors.forename: Francisco
authors.initials: F
authors.lastname: Ciruela
authors.forename: Carmen
authors.initials: C
authors.lastname: Lluis
authors.forename: Enric I
authors.initials: EI
authors.lastname: Canela
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D002462:Cell Membrane / Q000737:chemistry* / Q000378:metabolism; D019281:Dimerization; D006801:Humans; D008024:Ligands; D008954:Models, Biological; D011485:Protein Binding; D011487:Protein Conformation; D011956:Receptors, Cell Surface / Q000737:chemistry* / Q000378:metabolism
chemical_list: D008024:Ligands; D011956:Receptors, Cell Surface