+Open data
-Basic information
Entry | Database: PDB / ID: 8f7q | ||||||||||||
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Title | Gi bound mu-opioid receptor in complex with beta-endorphin | ||||||||||||
Components |
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Keywords | SIGNALING PROTEIN / mu opioid receptor / G protein coupled receptor / beta-endorphin | ||||||||||||
Function / homology | Function and homology information cellular pigmentation / positive regulation of oxytocin production / Peptide hormone biosynthesis / Defective ACTH causes obesity and POMCD / type 1 melanocortin receptor binding / type 3 melanocortin receptor binding / type 4 melanocortin receptor binding / regulation of corticosterone secretion / response to melanocyte-stimulating hormone / Opioid Signalling ...cellular pigmentation / positive regulation of oxytocin production / Peptide hormone biosynthesis / Defective ACTH causes obesity and POMCD / type 1 melanocortin receptor binding / type 3 melanocortin receptor binding / type 4 melanocortin receptor binding / regulation of corticosterone secretion / response to melanocyte-stimulating hormone / Opioid Signalling / beta-endorphin receptor activity / morphine receptor activity / negative regulation of Wnt protein secretion / Androgen biosynthesis / regulation of appetite / Glucocorticoid biosynthesis / regulation of cellular response to stress / G protein-coupled opioid receptor signaling pathway / regulation of glycogen metabolic process / behavioral response to ethanol / positive regulation of cAMP-mediated signaling / adenylate cyclase-inhibiting G protein-coupled acetylcholine receptor signaling pathway / sensory perception / negative regulation of nitric oxide biosynthetic process / negative regulation of cAMP-mediated signaling / 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 / Ca2+ pathway / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / neuropeptide binding / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / 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 / regulation of NMDA receptor activity / Thrombin signalling through proteinase activated receptors (PARs) / G alpha (i) signalling events / 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 / Adrenaline,noradrenaline inhibits insulin secretion / G alpha (12/13) signalling events / G beta:gamma signalling through BTK / ADP signalling through P2Y purinoceptor 12 / alkylglycerophosphoethanolamine phosphodiesterase activity / 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 / positive regulation of neurogenesis / G alpha (q) signalling events / photoreceptor outer segment membrane / G alpha (i) signalling events / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / positive regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway / spectrin binding / Vasopressin regulates renal water homeostasis via Aquaporins / negative regulation of cytosolic calcium ion concentration / G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / negative regulation of tumor necrosis factor production / neuropeptide signaling pathway / Transcriptional and post-translational regulation of MITF-M expression and activity / photoreceptor outer segment / G-protein alpha-subunit binding / T cell migration / voltage-gated calcium channel activity / Adenylate cyclase inhibitory pathway / positive regulation of protein localization to cell cortex / Endogenous sterols / FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes / regulation of cAMP-mediated signaling / D2 dopamine receptor binding / G protein-coupled serotonin receptor binding / MECP2 regulates neuronal receptors and channels / regulation of mitotic spindle organization / cardiac muscle cell apoptotic process / cellular response to forskolin / sensory perception of pain / photoreceptor inner segment / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / G-protein beta/gamma-subunit complex binding 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: 3.22 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 | 8f7q.cif.gz | 289.4 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8f7q.ent.gz | 223.8 KB | Display | PDB format |
PDBx/mmJSON format | 8f7q.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8f7q_validation.pdf.gz | 1.7 MB | Display | wwPDB validaton report |
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Full document | 8f7q_full_validation.pdf.gz | 1.8 MB | Display | |
Data in XML | 8f7q_validation.xml.gz | 48.7 KB | Display | |
Data in CIF | 8f7q_validation.cif.gz | 72.6 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/f7/8f7q ftp://data.pdbj.org/pub/pdb/validation_reports/f7/8f7q | HTTPS FTP |
-Related structure data
Related structure data | 28907MC 8f7rC 8f7sC 8f7wC 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, 4 molecules AFBC
#3: 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 | | 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 |
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-Protein / Protein/peptide / Antibody / Non-polymers , 4 types, 15 molecules RMPQE
#1: Protein | Mass: 45518.719 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: OPRM1, MOR1 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P35372 #2: Protein/peptide | Mass: 3470.022 Da / Num. of mol.: 2 / Fragment: UNP residues 237-267 / Source method: obtained synthetically / Source: (synth.) Homo sapiens (human) / References: UniProt: P01189 #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: Spodoptera frugiperda (fall armyworm) #7: Chemical | ChemComp-CLR / |
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-Details
Has ligand of interest | N |
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Has protein modification | Y |
-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: #1-#6 / 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: 3.22 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 320047 / Symmetry type: POINT |