Mutational analysis of the structure and function of opioid receptors

The cloning of the opioid receptors allows the investigation of receptor do mains involved in the peptidic and nonpeptidic ligand interaction and activ ation of the opioid receptors. Receptor chimera studies and mutational anal ysis of the primary sequences of rite opioid receptors have provided insigh ts into the structural domains required for the ligand recognition and rece ptor activation. In the current review, we examine the current reports on t he possible involvement of extracellular domains and transmembrane domains in the high-affinity binding of peptidic and nonpeptidic ligands to the opi oid receptor. The structural requirement for the receptors' selectivity tow ard different ligands is discussed. The receptor domains involved in the ac tivation and subsequent cellular regulation of the receptors' activities as determined hy mutational analysis will also be discussed Finally, the vali dity of the conclusions based on single amino acid mutations is examined. ( C) 2000 John Wiley & Sons, Inc.