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Structure paper

TitleStructures of the entire human opioid receptor family.
Journal, issue, pagesCell, Vol. 186, Issue 2, Page 413-427.e17, Year 2023
Publish dateJan 19, 2023
AuthorsYue Wang / Youwen Zhuang / Jeffrey F DiBerto / X Edward Zhou / Gavin P Schmitz / Qingning Yuan / Manish K Jain / Weiyi Liu / Karsten Melcher / Yi Jiang / Bryan L Roth / H Eric Xu /
PubMed AbstractOpioids 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 ...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.
External linksCell / PubMed:36638794
MethodsEM (single particle)
Resolution3.0 - 3.28 Å
Structure data

28907

8f7q

EMDB-28907, PDB-8f7q:
Gi bound mu-opioid receptor in complex with beta-endorphin
Method: EM (single particle) / Resolution: 3.22 Å

28908

8f7r

EMDB-28908, PDB-8f7r:
Gi bound mu-opioid receptor in complex with endomorphin
Method: EM (single particle) / Resolution: 3.28 Å

28909

8f7s

EMDB-28909, PDB-8f7s:
Gi bound delta-opioid receptor in complex with deltorphin
Method: EM (single particle) / Resolution: 3.0 Å

28911

8f7w

EMDB-28911, PDB-8f7w:
Gi bound kappa-opioid receptor in complex with dynorphin
Method: EM (single particle) / Resolution: 3.19 Å

28912

8f7x

EMDB-28912, PDB-8f7x:
Gi bound nociceptin receptor in complex with nociceptin peptide
Method: EM (single particle) / Resolution: 3.28 Å

Chemicals

ChemComp-CLR:
CHOLESTEROL / Cholesterol

ChemComp-PLM:
PALMITIC ACID / Palmitic acid

Source
  • homo sapiens (human)
  • rattus norvegicus (Norway rat)
  • bos taurus (cattle)
  • synthetic construct (others)
  • phyllomedusa (leaf frogs)
KeywordsSIGNALING PROTEIN / mu opioid receptor / G protein coupled receptor / beta-endorphin / endomorphin / delta opioid receptor / deltorphin / kappa opioid receptor / dynorphin

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