MOLECULAR MECHANISMS INVOLVED IN THE ACTIVATION AND REGULATION OF THEALPHA(1)-ADRENERGIC RECEPTOR SUBTYPES

The adrenergic receptors (ARs) belong to the superfamily of membrane-b ound G protein coupled receptors (GPCRs). Our investigation has focuse d on the structure-function relationship of the alpha(1b)-AR subtype u sed as the model system for other GPCRs. Site-directed mutagenesis stu dies have elucidated the structural domains of the alpha(1b)-AR involv ed in ligand binding, G protein coupling or desensitization. In additi on, a combined approach using site-directed mutagenesis and molecular dynamics analysis of the alpha(1b)-AR has provided information about t he potential mechanisms underlying the activation process of the recep tor, i.e. its transition from the 'inactive' to the 'active' conformat ion. (C) 1998 Elsevier Science S.A. All rights reserved.