The nociceptin (ORL1) receptor: molecular cloning and functional architecture.
Nociceptin and the ORL1 receptor share high sequence similarity with opioid peptides, particularly dynorphin A, and their receptors. However, nociceptin and dynorphin A may use distinct molecular pathways to bind and activate their cognate receptors. Activation of the kappa-opioid receptor by dynorphin A is thought to require interactions of its N-terminal hydrophobic domain (Y(1)GGF) with the receptor opioid binding pocket, located within the transmembrane helix bundle, while activation of the ORL1 receptor appears to require interactions of the positively charged core (R(8)KSARK) of nociceptin with the negatively charged second extracellular receptor loop.
Meunier
J
J
Institut de Pharmacologie et de Biologie Structurale, Centre National de la Recherche Scientifique, 205 route de Narbonne, 31077 cédex 4, Toulouse, France. jcm@ipbs.fr
Mouledous
L
L
Topham
C M
CM
D000595:Amino Acid Sequence; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D003001:Cloning, Molecular; D004399:Dynorphins / Q000737:chemistry; D006801:Humans; D008024:Ligands; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011957:Receptors, Opioid / Q000737:chemistry* / Q000235:genetics*; D017386:Sequence Homology, Amino Acid; D000094942:Nociceptin Receptor
D008024:Ligands; D010455:Peptides; D011957:Receptors, Opioid; D004399:Dynorphins; D000094942:Nociceptin Receptor; C000722283:OPRL1 protein, human