Mapping the functional domains of the beta-adrenergic receptor

The beta-adrenergic receptor (beta AR) serves as a model system for analysis of the structure-function relationships of G-protein-coupled receptors. Genetic analysis of the beta AR has demonstrated that the ligand-binding domain of this protein lies within the hydrophobic putative transmembrane core, involving specific amino acid residues in several of the transmembrane helices of the receptor. Site-directed mutagenesis of the receptor in conjunction with structural alterations of the ligands has revealed specific molecular interactions that are important for recognition of the ligand by the receptor. In addition, cytoplasmically exposed regions of the beta AR that are required for the activation of Gs have been identified. Because of the structural similarities among G-protein-coupled receptors, information gained from genetic analysis of the beta AR should prove useful in the development of specific agonists and antagonists for other receptors of this class.