Structure of the adrenergic and related receptors

Abstract

The isolation and sequencing of a number of G protein-coupled receptors has now provided extensive primary structure information for this family of homologous proteins. The diverse nature of these receptors suggests that the family of proteins may grow to include receptors for many neurotransmitters and perhaps many peptide hormones. The topography of these receptors, a single polypeptide with seven transmembrane segments, appears to have features well suited for the transmission of signals, via conformational changes, to the interior of the cell. Detailed site-directed mutagenesis studies are now underway in many laboratories to understand the significance of the topography and also the regions of homology evident in the structures of all of these receptors. Obvious features of interest are the precise residues involved in the coupling of the receptors to the G-proteins and the identification of the residues required for ligand binding in each of the receptors, as well as domains of these receptors involved in the regulation of receptor function. In addition, the availability of molecular probes for this family of proteins will permit the elucidation of mechanisms of regulation at the gene level.