title: Family C 7TM receptor dimerization and activation.
abstract: The family C seven transmembrane (7TM) receptors constitutes a small and especially well characterized subfamily of the large 7TM receptor superfamily. Approximately 50% of current prescription drugs target 7TM receptors, this biologically important family represents the largest class of drug-targets today. It is well established that family C 7TM receptors form homo- or hetero-dimers on the cell surface of living cells. The large extra-cellular domains (ECD) have been crystallized as a dimer in the presence and absence of agonist. Upon agonist binding, the dimeric ECD undergoes large conformational changes that lead to receptor activation. Despite extensive studies of the receptor transmembrane domain, several key features, including the exact organization of the complete receptor dimer, the sequence of events leading to receptor activation, and the functional significance of dimerization, have yet to be fully defined. This review presents the biochemical support for family C 7TM receptor dimerization and discusses its importance for receptor biosynthesis, surface expression, ligand binding and activation, since lessons learnt here may well be applicable to the whole superfamily of 7TM receptors.
authors.affiliation: Laboratory of Molecular and Cellular Cardiology, Danish Arrhythmia Research Centre (DARC), Copenhagen University Hospital section 9312, Denmark.
authors.forename: Marie Mi
authors.initials: MM
authors.lastname: Bonde
authors.forename: Søren P
authors.initials: SP
authors.lastname: Sheikh
authors.forename: Jakob Lerche
authors.initials: JL
authors.lastname: Hansen
mesh_terms: D000818:Animals; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000737:chemistry* / Q000187:drug effects*; D006801:Humans; D008024:Ligands; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: C505032:CFTR protein, human; D008024:Ligands; D043562:Receptors, G-Protein-Coupled; D019005:Cystic Fibrosis Transmembrane Conductance Regulator