Ligand and G-protein selectivity in the κ-opioid receptor.
Nature May 1, 2023 Jianming Han, Jingying Zhang, Antonina L Nazarova et al. 79 citations
Treatments for pain or addiction targeting the κ-opioid receptor often cause hallucinogenic side effects. To understand this, cryo-electron microscopy mapped the receptor's structure with various G-proteins and compounds. These detailed maps uncovered molecular controls for G-protein binding and drug selectivity, showing distinct preferences. This clarifies opioid action, establishing a foundation for developing safer, pathway-selective therapies.