+Open data
-Basic information
Entry | Database: PDB / ID: 8f7x | ||||||||||||
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Title | Gi bound nociceptin receptor in complex with nociceptin peptide | ||||||||||||
Components |
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Keywords | SIGNALING PROTEIN / mu opioid receptor / G protein coupled receptor / beta-endorphin | ||||||||||||
Function / homology | Function and homology information nociceptin receptor activity / opioid receptor binding / opioid peptide activity / neuron-neuron synaptic transmission / regulation of locomotor rhythm / sensory perception / negative regulation of cAMP-mediated signaling / positive regulation of urine volume / negative regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway / neuropeptide hormone activity ...nociceptin receptor activity / opioid receptor binding / opioid peptide activity / neuron-neuron synaptic transmission / regulation of locomotor rhythm / sensory perception / negative regulation of cAMP-mediated signaling / positive regulation of urine volume / negative regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway / neuropeptide hormone activity / conditioned place preference / 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 / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / Ca2+ pathway / G alpha (z) signalling events / Vasopressin regulates renal water homeostasis via Aquaporins / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / neuropeptide binding / Adrenaline,noradrenaline inhibits insulin secretion / ADP signalling through P2Y purinoceptor 12 / G alpha (q) signalling events / Thrombin signalling through proteinase activated receptors (PARs) / G alpha (i) signalling events / alkylglycerophosphoethanolamine phosphodiesterase activity / 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 / G alpha (12/13) signalling events / G beta:gamma signalling through BTK / ADP signalling through P2Y purinoceptor 12 / Adrenaline,noradrenaline inhibits insulin secretion / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / Thrombin signalling through proteinase activated receptors (PARs) / Ca2+ pathway / Extra-nuclear estrogen signaling / G alpha (z) signalling events / G alpha (s) signalling events / G alpha (q) signalling events / photoreceptor outer segment membrane / eating behavior / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / G alpha (i) signalling events / spectrin binding / Vasopressin regulates renal water homeostasis via Aquaporins / photoreceptor outer segment / neuropeptide signaling pathway / T cell migration / estrous cycle / D2 dopamine receptor binding / Adenylate cyclase inhibitory pathway / positive regulation of protein localization to cell cortex / regulation of cAMP-mediated signaling / G protein-coupled serotonin receptor binding / cellular response to forskolin / axon terminus / regulation of mitotic spindle organization / cardiac muscle cell apoptotic process / negative regulation of blood pressure / sensory perception of pain / photoreceptor inner segment / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / Peptide ligand-binding receptors / synaptic membrane / Regulation of insulin secretion / female pregnancy / G protein-coupled receptor binding / G protein-coupled receptor activity / calcium-mediated signaling / G-protein beta/gamma-subunit complex binding / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / response to peptide hormone / ADP signalling through P2Y purinoceptor 12 / Adrenaline,noradrenaline inhibits insulin secretion / G alpha (z) signalling events / cellular response to catecholamine stimulus / ADORA2B mediated anti-inflammatory cytokines production / sensory perception of taste / adenylate cyclase-activating dopamine receptor signaling pathway / GPER1 signaling / GDP binding / cellular response to prostaglandin E stimulus / G-protein beta-subunit binding / heterotrimeric G-protein complex / signaling receptor complex adaptor activity Similarity search - Function | ||||||||||||
Biological species | Homo sapiens (human) Rattus norvegicus (Norway rat) Bos taurus (cattle) synthetic construct (others) | ||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.28 Å | ||||||||||||
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. ...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
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Citation | Journal: 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 |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8f7x.cif.gz | 215 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8f7x.ent.gz | 165.4 KB | Display | PDB format |
PDBx/mmJSON format | 8f7x.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8f7x_validation.pdf.gz | 1.2 MB | Display | wwPDB validaton report |
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Full document | 8f7x_full_validation.pdf.gz | 1.2 MB | Display | |
Data in XML | 8f7x_validation.xml.gz | 38.8 KB | Display | |
Data in CIF | 8f7x_validation.cif.gz | 58.2 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/f7/8f7x ftp://data.pdbj.org/pub/pdb/validation_reports/f7/8f7x | HTTPS FTP |
-Related structure data
Related structure data | 28912MC 8f7qC 8f7rC 8f7sC 8f7wC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
-Guanine nucleotide-binding protein ... , 3 types, 3 molecules ABC
#3: Protein | Mass: 40445.059 Da / Num. of mol.: 1 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 |
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#4: Protein | 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 | 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 |
-Protein / Protein/peptide / Antibody , 3 types, 3 molecules RPE
#1: Protein | Mass: 40597.887 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: OPRL1, OOR, ORL1 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P41146 |
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#2: Protein/peptide | Mass: 1499.760 Da / Num. of mol.: 1 / Fragment: UNP residues 130-143 / Source method: obtained synthetically / Source: (synth.) Homo sapiens (human) / References: UniProt: Q13519 |
#6: Antibody | Mass: 26408.492 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) synthetic construct (others) / Production host: Escherichia coli (E. coli) |
-Details
Has protein modification | Y |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: Gi bound mu-opioid receptor in complex with beta-endorphin Type: COMPLEX / Entity ID: all / Source: MULTIPLE SOURCES |
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Source (natural) | Organism: Homo sapiens (human) |
Source (recombinant) | Organism: Spodoptera frugiperda (fall armyworm) |
Buffer solution | pH: 7.2 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 1800 nm / Nominal defocus min: 800 nm |
Image recording | Electron dose: 23.3 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
-Processing
Software | Name: PHENIX / Version: 1.13_2998: / Classification: refinement |
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CTF correction | Type: NONE |
3D reconstruction | Resolution: 3.28 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 184353 / Symmetry type: POINT |