6DDF

Mu Opioid Receptor-Gi Protein Complex

Summary for 6DDF

• Entry DOI: 10.2210/pdb6ddf/pdb
• Related: 6DDE
• EMDB information: 7868 7869
• Related PRD ID: PRD_002308
• Descriptor: Guanine nucleotide-binding protein G(i) subunit alpha-1, Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1, Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2, ... (5 entities in total)
• Functional Keywords: complex, transmembrane, membrane protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 5
• Total formula weight: 126455.97

Authors

Koehl, A.,Hu, H.,Maeda, S.,Manglik, A.,Kobilka, B.K.,Skiniotis, G.,Weis, W.I. (deposition date: 2018-05-10, release date: 2018-06-13, Last modification date: 2024-10-30)

Primary citation

Koehl, A.,Hu, H.,Maeda, S.,Zhang, Y.,Qu, Q.,Paggi, J.M.,Latorraca, N.R.,Hilger, D.,Dawson, R.,Matile, H.,Schertler, G.F.X.,Granier, S.,Weis, W.I.,Dror, R.O.,Manglik, A.,Skiniotis, G.,Kobilka, B.K.
Structure of the mu-opioid receptor-Giprotein complex.
Nature, 558:547-552, 2018

PubMed Abstract: The μ-opioid receptor (μOR) is a G-protein-coupled receptor (GPCR) and the target of most clinically and recreationally used opioids. The induced positive effects of analgesia and euphoria are mediated by μOR signalling through the adenylyl cyclase-inhibiting heterotrimeric G protein G. Here we present the 3.5 Å resolution cryo-electron microscopy structure of the μOR bound to the agonist peptide DAMGO and nucleotide-free G. DAMGO occupies the morphinan ligand pocket, with its N terminus interacting with conserved receptor residues and its C terminus engaging regions important for opioid-ligand selectivity. Comparison of the μOR-G complex to previously determined structures of other GPCRs bound to the stimulatory G protein G reveals differences in the position of transmembrane receptor helix 6 and in the interactions between the G protein α-subunit and the receptor core. Together, these results shed light on the structural features that contribute to the G protein-coupling specificity of the µOR.

PubMed: 29899455
DOI: 10.1038/s41586-018-0219-7

Experimental method

ELECTRON MICROSCOPY (3.5 Å)