8F7Q

Gi bound mu-opioid receptor in complex with beta-endorphin

Summary for 8F7Q

• Entry DOI: 10.2210/pdb8f7q/pdb
• EMDB information: 28907 28908 28909 28911 28912
• Descriptor: Mu-type opioid receptor, Beta-endorphin, Guanine nucleotide-binding protein G(i) subunit alpha-1, ... (7 entities in total)
• Functional Keywords: mu opioid receptor, g protein coupled receptor, beta-endorphin, signaling protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 9
• Total formula weight: 255727.05

Authors

Wang, Y.,Zhuang, Y.,DiBerto, J.F.,Zhou, X.E.,Schmitz, G.P.,Yuan, Q.,Jain, M.K.,Liu, W.,Melcher, K.,Jiang, Y.,Roth, B.L.,Xu, H.E. (deposition date: 2022-11-20, release date: 2022-12-14, Last modification date: 2025-05-21)

Primary citation

Wang, Y.,Zhuang, Y.,DiBerto, J.F.,Zhou, X.E.,Schmitz, G.P.,Yuan, Q.,Jain, M.K.,Liu, W.,Melcher, K.,Jiang, Y.,Roth, B.L.,Xu, H.E.
Structures of the entire human opioid receptor family.
Cell, 186:413-427.e17, 2023

PubMed Abstract: Opioids are effective analgesics, but their use is beset by serious side effects, including addiction and respiratory depression, which contribute to the ongoing opioid crisis. The human opioid system contains four opioid receptors (μOR, δOR, κOR, and NOPR) and a set of related endogenous opioid peptides (EOPs), which show distinct selectivity toward their respective opioid receptors (ORs). Despite being key to the development of safer analgesics, the mechanisms of molecular recognition and selectivity of EOPs to ORs remain unclear. Here, we systematically characterize the binding of EOPs to ORs and present five structures of EOP-OR-G complexes, including β-endorphin- and endomorphin-bound μOR, deltorphin-bound δOR, dynorphin-bound κOR, and nociceptin-bound NOPR. These structures, supported by biochemical results, uncover the specific recognition and selectivity of opioid peptides and the conserved mechanism of opioid receptor activation. These results provide a structural framework to facilitate rational design of safer opioid drugs for pain relief.

PubMed: 36638794
DOI: 10.1016/j.cell.2022.12.026

Experimental method

ELECTRON MICROSCOPY (3.22 Å)