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Open data
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Basic information
Entry | Database: PDB / ID: 8ef5 | ||||||||||||
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Title | Fentanyl-bound mu-opioid receptor-Gi complex | ||||||||||||
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![]() | SIGNALING PROTEIN / mu-opioid receptor / G protein / fentanyl | ||||||||||||
Function / homology | ![]() Opioid Signalling / beta-endorphin receptor activity / morphine receptor activity / negative regulation of Wnt protein secretion / regulation of cellular response to stress / G protein-coupled opioid receptor signaling pathway / behavioral response to ethanol / positive regulation of cAMP-mediated signaling / adenylate cyclase-inhibiting G protein-coupled acetylcholine receptor signaling pathway / sensory perception ...Opioid Signalling / beta-endorphin receptor activity / morphine receptor activity / negative regulation of Wnt protein secretion / regulation of cellular response to stress / G protein-coupled opioid receptor signaling pathway / 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 / 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 / Ca2+ pathway / 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 / G alpha (q) signalling events / positive regulation of neurogenesis / photoreceptor outer segment membrane / G alpha (i) signalling events / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / 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 / neuropeptide signaling pathway / photoreceptor outer segment / G-protein alpha-subunit binding / voltage-gated calcium channel activity / Adenylate cyclase inhibitory pathway / positive regulation of protein localization to cell cortex / 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 / cellular response to forskolin / cardiac muscle cell apoptotic process / sensory perception of pain / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / photoreceptor inner segment / Peptide ligand-binding receptors / Regulation of insulin secretion / G protein-coupled receptor binding / G protein-coupled receptor activity / G-protein beta/gamma-subunit complex binding / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / G-protein activation / 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 / cellular response to prostaglandin E stimulus / GPER1 signaling / GDP binding / G-protein beta-subunit binding / heterotrimeric G-protein complex Similarity search - Function | ||||||||||||
Biological species | ![]() ![]() ![]() ![]() ![]() synthetic construct (others) | ||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.3 Å | ||||||||||||
![]() | Zhuang, Y. / Wang, Y. / Guo, S. / Zhou, X.E. / Rao, Q. / He, X. / He, B. / Liu, J. / Zhou, Q. / Wang, X. ...Zhuang, Y. / Wang, Y. / Guo, S. / Zhou, X.E. / Rao, Q. / He, X. / He, B. / Liu, J. / Zhou, Q. / Wang, X. / Liu, W. / Jiang, X. / Yang, D. / Chen, X. / Jiang, Y. / Jiang, H. / Shen, J. / Melcher, K. / Wang, M. / Xie, X. / Xu, H.E. | ||||||||||||
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![]() | ![]() Title: Molecular recognition of morphine and fentanyl by the human μ-opioid receptor. Authors: Youwen Zhuang / Yue Wang / Bingqing He / Xinheng He / X Edward Zhou / Shimeng Guo / Qidi Rao / Jiaqi Yang / Jinyu Liu / Qingtong Zhou / Xiaoxi Wang / Mingliang Liu / Weiyi Liu / Xiangrui ...Authors: Youwen Zhuang / Yue Wang / Bingqing He / Xinheng He / X Edward Zhou / Shimeng Guo / Qidi Rao / Jiaqi Yang / Jinyu Liu / Qingtong Zhou / Xiaoxi Wang / Mingliang Liu / Weiyi Liu / Xiangrui Jiang / Dehua Yang / Hualiang Jiang / Jingshan Shen / Karsten Melcher / Hong Chen / Yi Jiang / Xi Cheng / Ming-Wei Wang / Xin Xie / H Eric Xu / ![]() ![]() Abstract: Morphine and fentanyl are among the most used opioid drugs that confer analgesia and unwanted side effects through both G protein and arrestin signaling pathways of μ-opioid receptor (μOR). Here, ...Morphine and fentanyl are among the most used opioid drugs that confer analgesia and unwanted side effects through both G protein and arrestin signaling pathways of μ-opioid receptor (μOR). Here, we report structures of the human μOR-G protein complexes bound to morphine and fentanyl, which uncover key differences in how they bind the receptor. We also report structures of μOR bound to TRV130, PZM21, and SR17018, which reveal preferential interactions of these agonists with TM3 side of the ligand-binding pocket rather than TM6/7 side. In contrast, morphine and fentanyl form dual interactions with both TM3 and TM6/7 regions. Mutations at the TM6/7 interface abolish arrestin recruitment of μOR promoted by morphine and fentanyl. Ligands designed to reduce TM6/7 interactions display preferential G protein signaling. Our results provide crucial insights into fentanyl recognition and signaling of μOR, which may facilitate rational design of next-generation analgesics. | ||||||||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 273.7 KB | Display | ![]() |
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PDB format | ![]() | 217.7 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 28066MC ![]() 8ef6C ![]() 8efbC ![]() 8eflC ![]() 8efoC ![]() 8efqC M: map data used to model this data C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
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Assembly
Deposited unit | ![]()
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Components
-Guanine nucleotide-binding protein ... , 3 types, 4 molecules AFBC
#2: Protein | Mass: 40445.059 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() #3: Protein | | Mass: 39020.664 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() #4: Protein | | Mass: 7563.750 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() |
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-Protein / Antibody , 2 types, 3 molecules RME
#1: Protein | Mass: 41072.191 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() #5: 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: ![]() ![]() |
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-Non-polymers , 2 types, 12 molecules ![](data/chem/img/7V7.gif)
![](data/chem/img/CLR.gif)
![](data/chem/img/CLR.gif)
#6: Chemical | #7: Chemical | ChemComp-CLR / |
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-Details
Has ligand of interest | 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 |
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Sample preparation
Component | Name: fentanyl bound mu-opioid receptor-G protein complex / Type: COMPLEX / Entity ID: #1-#5 / Source: MULTIPLE SOURCES |
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Source (natural) | Organism: ![]() |
Source (recombinant) | Organism: ![]() ![]() |
Buffer solution | pH: 7.2 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
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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: ![]() |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 5000 nm / Nominal defocus min: 3000 nm |
Image recording | Electron dose: 70 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
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Processing
Software | Name: PHENIX / Version: 1.13_2998: / Classification: refinement |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
3D reconstruction | Resolution: 3.3 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 291861 / Symmetry type: POINT |