[Structure of mu and delta opioid receptors].
The opioid receptor family is composed of three members, the µ, δ and κ opioid receptors, that respond to classical opioid alkaloids such as morphine and heroin as well as endogenous peptide ligands like endorphins. They belong to the G-protein-coupled receptor (GPCR) superfamily, and are excellent therapeutic targets for pain control. I will discuss new insights into conserved elements of opioid ligand recognition and structural features associated with ligand subtype selectivity based on the crystal structures we obtained for µ-OR and δ-OR. These data also provide a structural explanation and validation for the "message-address" model of opioid receptor pharmacology in which distinct "message" (efficacy) and "address" (selectivity) determinants are contained within a single ligand. Comparison of the "address" region of the OR with other GPCRs reveals this structural organization may be a more general phenomenon, extending to other GPCR families as well. Finally, I will discuss the µ-OR oligomeric arrangement in the crystal structure and its potential implication in opioid receptor function.
Institut de génomique fonctionnelle, Montpellier Cedex 5, France. sebastien.granier@igf.cnrs.fr
Sébastien
S
Granier
D000818:Animals; D017124:Conserved Sequence / Q000502:physiology; D006801:Humans; D008958:Models, Molecular; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs / Q000235:genetics; D055503:Protein Multimerization / Q000235:genetics / Q000502:physiology; D020836:Protein Structure, Quaternary / Q000502:physiology; D017465:Receptors, Opioid, delta / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D013379:Substrate Specificity
D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu