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Yorodumi- EMDB-28912: Gi bound nociceptin receptor in complex with nociceptin peptide -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-28912 | ||||||||||||
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Title | Gi bound nociceptin receptor in complex with nociceptin peptide | ||||||||||||
Map data | |||||||||||||
Sample |
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Function / homology | Function and homology information nociceptin receptor activity / opioid receptor binding / opioid peptide activity / 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 ...nociceptin receptor activity / opioid receptor binding / opioid peptide activity / 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 / 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 / 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 / photoreceptor outer segment membrane / G alpha (i) signalling events / eating behavior / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / spectrin binding / Vasopressin regulates renal water homeostasis via Aquaporins / neuropeptide signaling pathway / estrous cycle / photoreceptor outer segment / T cell migration / 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 / axon terminus / regulation of mitotic spindle organization / cardiac muscle cell apoptotic process / cellular response to forskolin / sensory perception of pain / negative regulation of blood pressure / photoreceptor inner segment / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / G-protein beta/gamma-subunit complex binding / Peptide ligand-binding receptors / Regulation of insulin secretion / female pregnancy / G protein-coupled receptor binding / G protein-coupled receptor activity / calcium-mediated signaling / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / response to peptide hormone / ADP signalling through P2Y purinoceptor 12 / G alpha (z) signalling events / Adrenaline,noradrenaline inhibits insulin secretion / ADORA2B mediated anti-inflammatory cytokines production / cellular response to catecholamine stimulus / sensory perception of taste / adenylate cyclase-activating dopamine receptor signaling pathway / GPER1 signaling / cellular response to prostaglandin E stimulus / GDP binding / G-protein beta-subunit binding / heterotrimeric G-protein complex / Hydrolases; Acting on acid anhydrides; Acting on GTP to facilitate cellular and subcellular movement / signaling receptor complex adaptor activity / response to estradiol 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: 3.28 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_28912.map.gz | 55.6 MB | EMDB map data format | |
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Header (meta data) | emd-28912-v30.xml emd-28912.xml | 20.6 KB 20.6 KB | Display Display | EMDB header |
Images | emd_28912.png | 127 KB | ||
Others | emd_28912_half_map_1.map.gz emd_28912_half_map_2.map.gz | 46.1 MB 46.1 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-28912 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-28912 | HTTPS FTP |
-Validation report
Summary document | emd_28912_validation.pdf.gz | 740.1 KB | Display | EMDB validaton report |
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Full document | emd_28912_full_validation.pdf.gz | 739.7 KB | Display | |
Data in XML | emd_28912_validation.xml.gz | 11.6 KB | Display | |
Data in CIF | emd_28912_validation.cif.gz | 13.3 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-28912 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-28912 | HTTPS FTP |
-Related structure data
Related structure data | 8f7xMC 8f7qC 8f7rC 8f7sC 8f7wC 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_28912.map.gz / Format: CCP4 / Size: 59.6 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 0.84 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: #2
File | emd_28912_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_28912_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: all |
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Source (natural) | Organism: Homo sapiens (human) |
-Macromolecule #1: Nociceptin receptor
Macromolecule | Name: Nociceptin 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: 40.597887 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
Sequence | String: EPLFPAPFWE VIYGSHLQGN LSLLSPNHSL LPPHLLLNAS HGAFLPLGLK VTIVGLYLAV CVGGLLGNCL VMYVILRHTK MKTATNIYI FNLALADTLV LLTLPFQGTD ILLGFWPFGN ALCKTVIAID YYNMFTSTFT LTAMSVDRYV AICHPIRALD V RTSSKAQA ...String: EPLFPAPFWE VIYGSHLQGN LSLLSPNHSL LPPHLLLNAS HGAFLPLGLK VTIVGLYLAV CVGGLLGNCL VMYVILRHTK MKTATNIYI FNLALADTLV LLTLPFQGTD ILLGFWPFGN ALCKTVIAID YYNMFTSTFT LTAMSVDRYV AICHPIRALD V RTSSKAQA VNVAIWALAS VVGVPVAIMG SAQVEDEEIE CLVEIPTPQD YWGPVFAICI FLFSFIVPVL VISVCYSLMI RR LRGVRLL SGSREKDRNL RRITRLVLVV VAVFVGCWTP VQVFVLAQGL GVQPSSETAV AILRFCTALG YVNSCLNPIL YAF LDENFK ACFRKFCCAS ALRRDVQVSD RVRSIAKDVA LACKTSETVP RPA |
-Macromolecule #2: Nociceptin
Macromolecule | Name: Nociceptin / 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: 1.49976 KDa |
Sequence | String: FGGFTGARKS ARKL |
-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 |
-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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Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 23.3 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 1.8 µm / Nominal defocus min: 0.8 µm |
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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Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.28 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 184353 |
Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |