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Structure paper

TitleStructure of the µ-opioid receptor-G protein complex.
Journal, issue, pagesNature, Vol. 558, Issue 7711, Page 547-552, Year 2018
Publish dateJun 13, 2018
AuthorsAntoine Koehl / Hongli Hu / Shoji Maeda / Yan Zhang / Qianhui Qu / Joseph M Paggi / Naomi R Latorraca / Daniel Hilger / Roger Dawson / Hugues Matile / Gebhard F X Schertler / Sebastien Granier / William I Weis / Ron O Dror / Aashish Manglik / Georgios Skiniotis / Brian K Kobilka /
PubMed AbstractThe 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 ...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.
External linksNature / PubMed:29899455 / PubMed Central
MethodsEM (single particle)
Resolution3.5 Å
Structure data

7868

6dde

EMDB-7868, PDB-6dde:
Mu Opioid Receptor-Gi Protein Complex
Method: EM (single particle) / Resolution: 3.5 Å

7869

6ddf

EMDB-7869, PDB-6ddf:
Mu Opioid Receptor-Gi Protein Complex
Method: EM (single particle) / Resolution: 3.5 Å

Source
  • homo sapiens (human)
  • mus musculus (house mouse)
KeywordsMEMBRANE PROTEIN / Complex / Transmembrane

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