+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-28911 | ||||||||||||
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Title | Gi bound kappa-opioid receptor in complex with dynorphin | ||||||||||||
Map data | |||||||||||||
Sample |
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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 / positive regulation of potassium ion transmembrane transport / sensory perception / 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 / 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 / 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 / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / hippocampal mossy fiber to CA3 synapse / 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 / synaptic vesicle membrane / ADP signalling through P2Y purinoceptor 12 Similarity search - Function | ||||||||||||
Biological species | Homo sapiens (human) / Rattus norvegicus (Norway rat) / Bos taurus (cattle) / synthetic construct (others) | ||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.19 Å | ||||||||||||
Authors | Wang Y / Zhuang Y / DiBerto JF / Zhou XE / Schmitz GP / Yuan Q / Jain MK / Liu W / Melcher K / Jiang Y ...Wang Y / Zhuang Y / DiBerto JF / Zhou XE / Schmitz GP / Yuan Q / Jain MK / Liu W / Melcher K / Jiang Y / Roth BL / Xu HE | ||||||||||||
Funding support | China, 3 items
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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
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_28911.map.gz | 28.4 MB | EMDB map data format | |
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Header (meta data) | emd-28911-v30.xml emd-28911.xml | 21.3 KB 21.3 KB | Display Display | EMDB header |
Images | emd_28911.png | 126.9 KB | ||
Others | emd_28911_half_map_1.map.gz emd_28911_half_map_2.map.gz | 23.3 MB 23.3 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-28911 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-28911 | HTTPS FTP |
-Related structure data
Related structure data | 8f7wMC 8f7qC 8f7rC 8f7sC 8f7xC C: citing same article (ref.) M: atomic model generated by this map |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_28911.map.gz / Format: CCP4 / Size: 30.5 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Voxel size | X=Y=Z: 1.071 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: #2
File | emd_28911_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_28911_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
-Entire : Gi bound mu-opioid receptor in complex with beta-endorphin
Entire | Name: Gi bound mu-opioid receptor in complex with beta-endorphin |
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Components |
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-Supramolecule #1: Gi bound mu-opioid receptor in complex with beta-endorphin
Supramolecule | Name: Gi bound mu-opioid receptor in complex with beta-endorphin type: complex / ID: 1 / Chimera: Yes / Parent: 0 / Macromolecule list: #2-#6, #1 |
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Source (natural) | Organism: Homo sapiens (human) |
-Macromolecule #1: Kappa-type opioid receptor
Macromolecule | Name: Kappa-type opioid receptor / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 42.434738 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
Sequence | String: SPIQIFRGEP GPTCAPSACL PPNSSAWFPG WAEPDSNGSA GSEDAQLEPA HISPAIPVII TAVYSVVFVV GLVGNSLVMF VIIRYTKMK TATNIYIFNL ALADALVTTT MPFQSTVYLM NSWPFGDVLC KIVISIDYYN MFTSIFTLTM MSVDRYIAVC H PVKALDFR ...String: SPIQIFRGEP GPTCAPSACL PPNSSAWFPG WAEPDSNGSA GSEDAQLEPA HISPAIPVII TAVYSVVFVV GLVGNSLVMF VIIRYTKMK TATNIYIFNL ALADALVTTT MPFQSTVYLM NSWPFGDVLC KIVISIDYYN MFTSIFTLTM MSVDRYIAVC H PVKALDFR TPLKAKIINI CIWLLSSSVG ISAIVLGGTK VREDVDVIEC SLQFPDDDYS WWDLFMKICV FIFAFVIPVL II IVCYTLM ILRLKSVRLL SGSREKDRNL RRITRLVLVV VAVFVVCWTP IHIFILVEAL GSTSHSTAAL SSYYFCIALG YTN SSLNPI LYAFLDENFK RCFRDFCFPL KMRMERQSTS RVRNTVQDPA YLRDIDGMNK PV |
-Macromolecule #2: Dynorphin
Macromolecule | Name: Dynorphin / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 983.169 Da |
Sequence | String: YGGFLRRI |
-Macromolecule #3: Guanine nucleotide-binding protein G(i) subunit alpha-1
Macromolecule | Name: Guanine nucleotide-binding protein G(i) subunit alpha-1 type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 40.445059 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
Sequence | String: MGCTLSAEDK AAVERSKMID RNLREDGEKA AREVKLLLLG AGESGKSTIV KQMKIIHEAG YSEEECKQYK AVVYSNTIQS IIAIIRAMG RLKIDFGDSA RADDARQLFV LAGAAEEGFM TAELAGVIKR LWKDSGVQAC FNRSREYQLN DSAAYYLNDL D RIAQPNYI ...String: MGCTLSAEDK AAVERSKMID RNLREDGEKA AREVKLLLLG AGESGKSTIV KQMKIIHEAG YSEEECKQYK AVVYSNTIQS IIAIIRAMG RLKIDFGDSA RADDARQLFV LAGAAEEGFM TAELAGVIKR LWKDSGVQAC FNRSREYQLN DSAAYYLNDL D RIAQPNYI PTQQDVLRTR VKTTGIVETH FTFKDLHFKM FDVGAQRSER KKWIHCFEGV TAIIFCVALS DYDLVLAEDE EM NRMHESM KLFDSICNNK WFTDTSIILF LNKKDLFEEK IKKSPLTICY PEYAGSNTYE EAAAYIQCQF EDLNKRKDTK EIY THFTCS TDTKNVQFVF DAVTDVIIKN NLKDCGLF |
-Macromolecule #4: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
Macromolecule | Name: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Rattus norvegicus (Norway rat) |
Molecular weight | Theoretical: 39.020664 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
Sequence | String: MHHHHHHHHG SLLQSELDQL RQEAEQLKNQ IRDARKACAD ATLSQITNNI DPVGRIQMRT RRTLRGHLAK IYAMHWGTDS RLLVSASQD GKLIIWDSYT TNKVHAIPLR SSWVMTCAYA PSGNYVACGG LDNICSIYNL KTREGNVRVS RELAGHTGYL S CCRFLDDN ...String: MHHHHHHHHG SLLQSELDQL RQEAEQLKNQ IRDARKACAD ATLSQITNNI DPVGRIQMRT RRTLRGHLAK IYAMHWGTDS RLLVSASQD GKLIIWDSYT TNKVHAIPLR SSWVMTCAYA PSGNYVACGG LDNICSIYNL KTREGNVRVS RELAGHTGYL S CCRFLDDN QIVTSSGDTT CALWDIETGQ QTTTFTGHTG DVMSLSLAPD TRLFVSGACD ASAKLWDVRE GMCRQTFTGH ES DINAICF FPNGNAFATG SDDATCRLFD LRADQELMTY SHDNIICGIT SVSFSKSGRL LLAGYDDFNC NVWDALKADR AGV LAGHDN RVSCLGVTDD GMAVATGSWD SFLKIWN |
-Macromolecule #5: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
Macromolecule | Name: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 type: protein_or_peptide / ID: 5 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Bos taurus (cattle) |
Molecular weight | Theoretical: 7.56375 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
Sequence | String: MASNNTASIA QARKLVEQLK MEANIDRIKV SKAAADLMAY CEAHAKEDPL LTPVPASENP FREKKFFC |
-Macromolecule #6: scFv16
Macromolecule | Name: scFv16 / type: protein_or_peptide / ID: 6 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: synthetic construct (others) |
Molecular weight | Theoretical: 26.408492 KDa |
Recombinant expression | Organism: Escherichia coli (E. coli) |
Sequence | String: MVQLVESGGG LVQPGGSRKL SCSASGFAFS SFGMHWVRQA PEKGLEWVAY ISSGSGTIYY ADTVKGRFTI SRDDPKNTLF LQMTSLRSE DTAMYYCVRS IYYYGSSPFD FWGQGTTLTV SAGGGGSGGG GSGGGGSADI VMTQATSSVP VTPGESVSIS C RSSKSLLH ...String: MVQLVESGGG LVQPGGSRKL SCSASGFAFS SFGMHWVRQA PEKGLEWVAY ISSGSGTIYY ADTVKGRFTI SRDDPKNTLF LQMTSLRSE DTAMYYCVRS IYYYGSSPFD FWGQGTTLTV SAGGGGSGGG GSGGGGSADI VMTQATSSVP VTPGESVSIS C RSSKSLLH SNGNTYLYWF LQRPGQSPQL LIYRMSNLAS GVPDRFSGSG SGTAFTLTIS RLEAEDVGVY YCMQHLEYPL TF GAGTKLE L |
-Macromolecule #7: CHOLESTEROL
Macromolecule | Name: CHOLESTEROL / type: ligand / ID: 7 / Number of copies: 3 / Formula: CLR |
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Molecular weight | Theoretical: 386.654 Da |
Chemical component information | ChemComp-CLR: |
-Macromolecule #8: PALMITIC ACID
Macromolecule | Name: PALMITIC ACID / type: ligand / ID: 8 / Number of copies: 2 / Formula: PLM |
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Molecular weight | Theoretical: 256.424 Da |
Chemical component information | ChemComp-PLM: |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.2 |
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Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy / Nominal defocus max: 1.8 µm / Nominal defocus min: 0.8 µm |
Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 23.3 e/Å2 |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Startup model | Type of model: PDB ENTRY PDB model - PDB ID: |
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Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.19 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 299465 |