AMINO-ACIDS OF THE ALPHA(1B)-ADRENERGIC RECEPTOR INVOLVED IN AGONIST BINDING - DIFFERENCES IN DOCKING CATECHOLAMINES TO RECEPTOR SUBTYPES

Site-directed mutagenesis and molecular dynamics analysis of the 3-D m odel of the alpha(1B)-adrenergic receptor (AR) were combined to identi fy the molecular determinants of the receptor involved in catecholamin e binding. Our results indicate that the three conserved serines in th e fifth transmembrane domain (TMD) of the alpha(1B)-AR play a distinct role in catecholamine binding versus receptor activation. In addition to the amino acids D125 in TMDIII and S207 in TMDV directly involved in ligand binding, our findings identify a large number of polar resid ues playing an important role in the activation process of the alpha(1 B)-AR thus providing new insights into the structure/function relation ship of G protein-coupled receptors.