+Open data
-Basic information
Entry | Database: PDB / ID: 8f7w | ||||||||||||
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Title | Gi bound kappa-opioid receptor in complex with dynorphin | ||||||||||||
Components |
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Keywords | SIGNALING PROTEIN / kappa opioid receptor / G protein coupled receptor / dynorphin | ||||||||||||
Function / homology | Function and homology information opioid receptor binding / opioid peptide activity / Opioid Signalling / dynorphin receptor activity / response to acrylamide / regulation of saliva secretion / negative regulation of luteinizing hormone secretion / positive regulation of eating behavior / sensory perception of temperature stimulus / adenylate cyclase-inhibiting opioid receptor signaling pathway ...opioid receptor binding / opioid peptide activity / Opioid Signalling / dynorphin receptor activity / response to acrylamide / regulation of saliva secretion / negative regulation of luteinizing hormone secretion / positive regulation of eating behavior / sensory perception of temperature stimulus / adenylate cyclase-inhibiting opioid receptor signaling pathway / G protein-coupled opioid receptor activity / conditioned place preference / G protein-coupled opioid receptor signaling pathway / positive regulation of dopamine secretion / sensory perception / positive regulation of potassium ion transmembrane transport / maternal behavior / 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 / positive regulation of p38MAPK cascade / 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 / behavioral response to cocaine / estrous cycle / photoreceptor outer segment / Adenylate cyclase inhibitory pathway / neuropeptide signaling pathway / positive regulation of protein localization to cell cortex / regulation of cAMP-mediated signaling / D2 dopamine receptor binding / G protein-coupled serotonin receptor binding / axon terminus / MECP2 regulates neuronal receptors and channels / regulation of mitotic spindle organization / cellular response to forskolin / sensory perception of pain / cardiac muscle cell apoptotic process / hippocampal mossy fiber to CA3 synapse / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / photoreceptor inner segment / Peptide ligand-binding receptors / locomotory behavior / Regulation of insulin secretion / G protein-coupled receptor binding / cellular response to glucose stimulus / G-protein beta/gamma-subunit complex binding / response to insulin / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / G-protein activation / ADP signalling through P2Y purinoceptor 12 / synaptic vesicle membrane 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: 3.19 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 | 8f7w.cif.gz | 213.7 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8f7w.ent.gz | 169.3 KB | Display | PDB format |
PDBx/mmJSON format | 8f7w.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/f7/8f7w ftp://data.pdbj.org/pub/pdb/validation_reports/f7/8f7w | HTTPS FTP |
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-Related structure data
Related structure data | 28911MC 8f7qC 8f7rC 8f7sC 8f7xC 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: 42434.738 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: OPRK1, OPRK / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P41145 |
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#2: Protein/peptide | Mass: 983.169 Da / Num. of mol.: 1 / Fragment: UNP residues 207-214 / Source method: obtained synthetically / Source: (synth.) Homo sapiens (human) / References: UniProt: P01213 |
#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) |
-Non-polymers , 2 types, 5 molecules
#7: Chemical | #8: Chemical | |
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-Details
Has ligand of interest | N |
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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: #2-#6, #1 / 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 FIELDBright-field microscopy / 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: 3.19 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 299465 / Symmetry type: POINT |