At top, a space-filling structure of the δ-opioid receptor bound to an antagonist (center), and at bottom a ribbon structure of the nociceptin receptor bound to an antagonist (spheres). Disks represent membrane surfaces.
Researchers have completed crystal structure analyses of the last of the four types of opioid receptors. These receptors are targets for antidepressants and pain and reward agents such as morphine. The structures were previously unavailable because opioid receptors, which are membrane proteins, would not form crystals. They were obtained through a technique that conjugates an opioid receptor to a crystallizable protein. This strategy led to antagonist-bound structures reported in March for the µ-opioid receptor by Brian K. Kobilka and Sébastien Granier of Stanford University and coworkers and the κ-opioid receptor by a group led by Raymond C. Stevens of Scripps Research Institute (C&EN, March 26, page 11). Now, the Stanford group has solved the δ-opioid receptor structure, and the Scripps team has reported the nociceptin (orphanin FQ) receptor structure, both bound to antagonists, rounding out the gang of four opioid receptor subtypes (Nature, DOI: 10.1038/nature11111 and 10.1038/nature11085). The crystal structures help elucidate how drugs bind the opioid receptors and could lead to optimization of the growing list of opioid therapeutics.