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- PDB-8f7s: Gi bound delta-opioid receptor in complex with deltorphin -

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Basic information

Entry
Database: PDB / ID: 8f7s
TitleGi bound delta-opioid receptor in complex with deltorphin
Components
  • (Guanine nucleotide-binding protein ...) x 3
  • Delta-type opioid receptor
  • deltorphin
KeywordsSIGNALING PROTEIN / delta opioid receptor / G protein coupled receptor / deltorphin
Function / homology
Function and homology information


G protein-coupled enkephalin receptor activity / opioid peptide activity / spine apparatus / positive regulation of CREB transcription factor activity / G protein-coupled opioid receptor activity / G protein-coupled opioid receptor signaling pathway / cellular response to toxic substance / neuropeptide binding / G-protein activation / Activation of the phototransduction cascade ...G protein-coupled enkephalin receptor activity / opioid peptide activity / spine apparatus / positive regulation of CREB transcription factor activity / G protein-coupled opioid receptor activity / G protein-coupled opioid receptor signaling pathway / cellular response to toxic substance / neuropeptide binding / G-protein activation / Activation of the phototransduction cascade / : / Glucagon-type ligand receptors / Thromboxane signalling through TP receptor / Sensory perception of sweet, bitter, and umami (glutamate) taste / G beta:gamma signalling through PI3Kgamma / G beta:gamma signalling through CDC42 / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / Ca2+ pathway / Activation of G protein gated Potassium channels / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / receptor serine/threonine kinase binding / G alpha (z) signalling events / Vasopressin regulates renal water homeostasis via Aquaporins / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / Adrenaline,noradrenaline inhibits insulin secretion / ADP signalling through P2Y purinoceptor 12 / G alpha (q) signalling events / G alpha (i) signalling events / Thrombin signalling through proteinase activated receptors (PARs) / Activation of G protein gated Potassium channels / G-protein activation / G beta:gamma signalling through PI3Kgamma / Prostacyclin signalling through prostacyclin receptor / G beta:gamma signalling through PLC beta / ADP signalling through P2Y purinoceptor 1 / Thromboxane signalling through TP receptor / Presynaptic function of Kainate receptors / G beta:gamma signalling through CDC42 / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / Glucagon-type ligand receptors / alkylglycerophosphoethanolamine phosphodiesterase activity / Adrenaline,noradrenaline inhibits insulin secretion / G alpha (12/13) signalling events / G beta:gamma signalling through BTK / ADP signalling through P2Y purinoceptor 12 / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / Thrombin signalling through proteinase activated receptors (PARs) / Ca2+ pathway / G alpha (z) signalling events / Extra-nuclear estrogen signaling / G alpha (s) signalling events / G alpha (q) signalling events / photoreceptor outer segment membrane / G alpha (i) signalling events / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / eating behavior / spectrin binding / Vasopressin regulates renal water homeostasis via Aquaporins / neuronal dense core vesicle / G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / regulation of calcium ion transport / photoreceptor outer segment / Adenylate cyclase inhibitory pathway / positive regulation of protein localization to cell cortex / neuropeptide signaling pathway / regulation of cAMP-mediated signaling / D2 dopamine receptor binding / G protein-coupled serotonin receptor binding / negative regulation of protein-containing complex assembly / axon terminus / regulation of mitotic spindle organization / cellular response to forskolin / cardiac muscle cell apoptotic process / dendrite membrane / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / photoreceptor inner segment / Peptide ligand-binding receptors / adult locomotory behavior / regulation of mitochondrial membrane potential / Regulation of insulin secretion / G protein-coupled receptor binding / postsynaptic density membrane / G-protein beta/gamma-subunit complex binding / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / defense response / synaptic vesicle membrane / ADP signalling through P2Y purinoceptor 12 / response to peptide hormone / cellular response to growth factor stimulus / Adrenaline,noradrenaline inhibits insulin secretion / G alpha (z) signalling events / cellular response to catecholamine stimulus / ADORA2B mediated anti-inflammatory cytokines production / adenylate cyclase-activating dopamine receptor signaling pathway / cellular response to prostaglandin E stimulus / sensory perception of taste / GPER1 signaling / GDP binding / G-protein beta-subunit binding
Similarity search - Function
Delta opioid receptor / Frog antimicrobial peptide, propeptide / Frog skin active peptide family signal and propeptide / Opioid receptor / G-protein alpha subunit, group I / Serpentine type 7TM GPCR chemoreceptor Srsx / G-alpha domain profile. / Guanine nucleotide binding protein (G-protein), alpha subunit / G protein alpha subunit, helical insertion / G-protein alpha subunit ...Delta opioid receptor / Frog antimicrobial peptide, propeptide / Frog skin active peptide family signal and propeptide / Opioid receptor / G-protein alpha subunit, group I / Serpentine type 7TM GPCR chemoreceptor Srsx / G-alpha domain profile. / Guanine nucleotide binding protein (G-protein), alpha subunit / G protein alpha subunit, helical insertion / G-protein alpha subunit / G protein alpha subunit / G-protein, gamma subunit / G-protein gamma subunit domain profile. / GGL domain / G-protein gamma-like domain superfamily / G-protein gamma-like domain / GGL domain / G protein gamma subunit-like motifs / Guanine nucleotide-binding protein, beta subunit / G-protein, beta subunit / G-protein coupled receptors family 1 signature. / G protein-coupled receptor, rhodopsin-like / GPCR, rhodopsin-like, 7TM / G-protein coupled receptors family 1 profile. / 7 transmembrane receptor (rhodopsin family) / G-protein beta WD-40 repeat / WD40 repeat, conserved site / Trp-Asp (WD) repeats signature. / WD domain, G-beta repeat / WD40 repeats / WD40 repeat / Trp-Asp (WD) repeats profile. / Trp-Asp (WD) repeats circular profile. / WD40-repeat-containing domain superfamily / WD40/YVTN repeat-like-containing domain superfamily / P-loop containing nucleoside triphosphate hydrolase
Similarity search - Domain/homology
CHOLESTEROL / PALMITIC ACID / [D-Ala2]-deltorphins / Delta-type opioid receptor / Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 / Guanine nucleotide-binding protein G(i) subunit alpha-1 / Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
Similarity search - Component
Biological speciesHomo sapiens (human)
Rattus norvegicus (Norway rat)
Bos taurus (cattle)
Phyllomedusa (leaf frogs)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3 Å
AuthorsWang, Y. / Zhuang, Y. / DiBerto, J.F. / Zhou, X.E. / Schmitz, G.P. / Yuan, Q. / Jain, M.K. / Liu, W. / Melcher, K. / Jiang, Y. ...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.
Funding support China, 3items
OrganizationGrant numberCountry
Ministry of Science and Technology (MoST, China)2018YFA0507002 China
National Natural Science Foundation of China (NSFC)82121005 China
Chinese Academy of SciencesXDB08020303 China
CitationJournal: Cell / Year: 2023
Title: Structures of the entire human opioid receptor family.
Authors: Yue 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 /
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 ...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.
History
DepositionNov 20, 2022Deposition site: RCSB / Processing site: RCSB
Revision 1.0Dec 14, 2022Provider: repository / Type: Initial release
Revision 1.1Jan 25, 2023Group: Database references / Category: citation / citation_author
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_ASTM / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year / _citation_author.identifier_ORCID
Revision 1.2Feb 1, 2023Group: Database references / Category: citation
Item: _citation.journal_volume / _citation.page_first / _citation.page_last

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

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Assembly

Deposited unit
R: Delta-type opioid receptor
P: deltorphin
A: Guanine nucleotide-binding protein G(i) subunit alpha-1
B: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
C: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
D: Delta-type opioid receptor
Q: deltorphin
F: Guanine nucleotide-binding protein G(i) subunit alpha-1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)219,35125
Polymers214,3408
Non-polymers5,01017
Water0
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_5551

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Components

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Guanine nucleotide-binding protein ... , 3 types, 4 molecules AFBC

#3: Protein Guanine nucleotide-binding protein G(i) subunit alpha-1 / Adenylate cyclase-inhibiting G alpha protein


Mass: 40445.059 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: GNAI1 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P63096
#4: Protein Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 / Transducin beta chain 1


Mass: 39020.664 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Rattus norvegicus (Norway rat) / Gene: Gnb1 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P54311
#5: Protein Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 / G gamma-I


Mass: 7563.750 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Bos taurus (cattle) / Gene: GNG2 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P63212

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Protein / Protein/peptide , 2 types, 4 molecules RDPQ

#1: Protein Delta-type opioid receptor / D-OR-1 / DOR-1


Mass: 42651.020 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: OPRD1, OPRD / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P41143
#2: Protein/peptide deltorphin / [D-Ala2]-deltorphin II


Mass: 781.876 Da / Num. of mol.: 2 / Fragment: UNP residues 107-113 / Source method: obtained synthetically / Source: (synth.) Phyllomedusa (leaf frogs) / References: UniProt: P21850

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Non-polymers , 2 types, 17 molecules

#6: Chemical
ChemComp-CLR / CHOLESTEROL / Cholesterol


Mass: 386.654 Da / Num. of mol.: 5 / Source method: obtained synthetically / Formula: C27H46O
#7: Chemical
ChemComp-PLM / PALMITIC ACID / Palmitic acid


Mass: 256.424 Da / Num. of mol.: 12 / Source method: obtained synthetically / Formula: C16H32O2

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Details

Has ligand of interestN

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Experimental details

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Experiment

ExperimentMethod: ELECTRON MICROSCOPY
EM experimentAggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction

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Sample preparation

ComponentName: Gi bound mu-opioid receptor in complex with beta-endorphin
Type: COMPLEX / Entity ID: #1-#5 / Source: MULTIPLE SOURCES
Source (natural)Organism: Homo sapiens (human)
Source (recombinant)Organism: Spodoptera frugiperda (fall armyworm)
Buffer solutionpH: 7.2
SpecimenEmbedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
VitrificationCryogen name: ETHANE

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Electron microscopy imaging

Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
MicroscopyModel: FEI TITAN KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELDBright-field microscopy / Nominal defocus max: 1800 nm / Nominal defocus min: 800 nm
Image recordingElectron dose: 23.3 e/Å2 / Film or detector model: GATAN K3 (6k x 4k)

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Processing

SoftwareName: PHENIX / Version: 1.13_2998: / Classification: refinement
CTF correctionType: NONE
3D reconstructionResolution: 3 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 650970 / Symmetry type: POINT

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