Amino acids of the α1B‐adrenergic receptor involved in agonist binding: differences in docking catecholamines to receptor subtypes

Abstract

Site-directed mutagenesis and molecular dynamics analysis of the 3-D model of the α _1B -adrenergic receptor (AR) were combined to identify the molecular determinants of the receptor involved in catecholamine binding. Our results indicate that the three conserved serines in the fifth transmembrane domain (TMD) of the α _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 residues playing an important role in the activation process of the α _1B-AR thus providing new insights into the structure/function relationship of G protein-coupled receptors.