+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-7869 | ||||||||||||||||||
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Title | Mu Opioid Receptor-Gi Protein Complex | ||||||||||||||||||
Map data | Mu Opioid Receptor-Gi Protein Complex, full map | ||||||||||||||||||
Sample |
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Keywords | Complex / Transmembrane / MEMBRANE PROTEIN | ||||||||||||||||||
Function / homology | Function and homology information Opioid Signalling / spine apparatus / beta-endorphin receptor activity / morphine receptor activity / negative regulation of Wnt protein secretion / Peptide ligand-binding receptors / adenylate cyclase-inhibiting opioid receptor signaling pathway / positive regulation of appetite / G-protein activation / G protein-coupled opioid receptor activity ...Opioid Signalling / spine apparatus / beta-endorphin receptor activity / morphine receptor activity / negative regulation of Wnt protein secretion / Peptide ligand-binding receptors / adenylate cyclase-inhibiting opioid receptor signaling pathway / positive regulation of appetite / G-protein activation / G protein-coupled opioid receptor activity / negative regulation of luteinizing hormone secretion / G protein-coupled opioid receptor signaling pathway / sperm ejaculation / G alpha (i) signalling events / adenylate cyclase-inhibiting G protein-coupled acetylcholine receptor signaling pathway / negative regulation of nitric oxide biosynthetic process / negative regulation of cAMP-mediated signaling / negative regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway / neuropeptide binding / regulation of NMDA receptor activity / positive regulation of neurogenesis / eating behavior / negative regulation of cytosolic calcium ion concentration / transmission of nerve impulse / social behavior / neuropeptide signaling pathway / 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 / regulation of cAMP-mediated signaling / D2 dopamine receptor binding / G protein-coupled serotonin receptor binding / GABA-ergic synapse / positive regulation of gluconeogenesis / regulation of mitotic spindle organization / sensory perception of pain / dendrite membrane / cellular response to forskolin / presynaptic modulation of chemical synaptic transmission / dendrite cytoplasm / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / excitatory postsynaptic potential / locomotory behavior / Regulation of insulin secretion / G protein-coupled receptor binding / G protein-coupled receptor activity / G-protein beta/gamma-subunit complex binding / Olfactory Signaling Pathway / Activation of the phototransduction cascade / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / G protein-coupled acetylcholine receptor signaling pathway / G-protein activation / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / Prostacyclin signalling through prostacyclin receptor / Glucagon signaling in metabolic regulation / response to peptide hormone / G beta:gamma signalling through CDC42 / G beta:gamma signalling through BTK / ADP signalling through P2Y purinoceptor 12 / Sensory perception of sweet, bitter, and umami (glutamate) taste / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / photoreceptor disc membrane / Glucagon-type ligand receptors / Adrenaline,noradrenaline inhibits insulin secretion / Vasopressin regulates renal water homeostasis via Aquaporins / G alpha (z) signalling events / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / cellular response to catecholamine stimulus / ADORA2B mediated anti-inflammatory cytokines production / sensory perception of taste / ADP signalling through P2Y purinoceptor 1 / G beta:gamma signalling through PI3Kgamma / adenylate cyclase-activating dopamine receptor signaling pathway / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / GPER1 signaling / GDP binding / cellular response to prostaglandin E stimulus / Inactivation, recovery and regulation of the phototransduction cascade / G-protein beta-subunit binding / heterotrimeric G-protein complex / G alpha (12/13) signalling events / extracellular vesicle / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / GTPase binding / retina development in camera-type eye / presynaptic membrane / Ca2+ pathway / phospholipase C-activating G protein-coupled receptor signaling pathway / cell cortex / midbody / fibroblast proliferation / G alpha (i) signalling events / G alpha (s) signalling events Similarity search - Function | ||||||||||||||||||
Biological species | Homo sapiens (human) / Mus musculus (house mouse) | ||||||||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.5 Å | ||||||||||||||||||
Authors | Koehl A / Hu H | ||||||||||||||||||
Funding support | United States, Switzerland, 5 items
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Citation | Journal: Nature / Year: 2018 Title: Structure of the µ-opioid receptor-G protein complex. Authors: Antoine Koehl / Hongli Hu / Shoji Maeda / Yan Zhang / Qianhui Qu / Joseph M Paggi / Naomi R Latorraca / Daniel Hilger / Roger Dawson / Hugues Matile / Gebhard F X Schertler / Sebastien ...Authors: Antoine Koehl / Hongli Hu / Shoji Maeda / Yan Zhang / Qianhui Qu / Joseph M Paggi / Naomi R Latorraca / Daniel Hilger / Roger Dawson / Hugues Matile / Gebhard F X Schertler / Sebastien Granier / William I Weis / Ron O Dror / Aashish Manglik / Georgios Skiniotis / Brian K Kobilka / Abstract: The μ-opioid receptor (μOR) is a G-protein-coupled receptor (GPCR) and the target of most clinically and recreationally used opioids. The induced positive effects of analgesia and euphoria are ...The μ-opioid receptor (μOR) is a G-protein-coupled receptor (GPCR) and the target of most clinically and recreationally used opioids. The induced positive effects of analgesia and euphoria are mediated by μOR signalling through the adenylyl cyclase-inhibiting heterotrimeric G protein G. Here we present the 3.5 Å resolution cryo-electron microscopy structure of the μOR bound to the agonist peptide DAMGO and nucleotide-free G. DAMGO occupies the morphinan ligand pocket, with its N terminus interacting with conserved receptor residues and its C terminus engaging regions important for opioid-ligand selectivity. Comparison of the μOR-G complex to previously determined structures of other GPCRs bound to the stimulatory G protein G reveals differences in the position of transmembrane receptor helix 6 and in the interactions between the G protein α-subunit and the receptor core. Together, these results shed light on the structural features that contribute to the G protein-coupling specificity of the µOR. | ||||||||||||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_7869.map.gz | 48.8 MB | EMDB map data format | |
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Header (meta data) | emd-7869-v30.xml emd-7869.xml | 24.6 KB 24.6 KB | Display Display | EMDB header |
Images | emd_7869.png | 58.7 KB | ||
Filedesc metadata | emd-7869.cif.gz | 7.3 KB | ||
Others | emd_7869_half_map_1.map.gz emd_7869_half_map_2.map.gz | 49.4 MB 49.5 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-7869 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-7869 | HTTPS FTP |
-Validation report
Summary document | emd_7869_validation.pdf.gz | 753.8 KB | Display | EMDB validaton report |
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Full document | emd_7869_full_validation.pdf.gz | 753.4 KB | Display | |
Data in XML | emd_7869_validation.xml.gz | 11.9 KB | Display | |
Data in CIF | emd_7869_validation.cif.gz | 13.6 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-7869 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-7869 | HTTPS FTP |
-Related structure data
Related structure data | 6ddfMC 7868C 6ddeC C: citing same article (ref.) M: atomic model generated by this map |
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Similar structure data |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_7869.map.gz / Format: CCP4 / Size: 52.7 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | Mu Opioid Receptor-Gi Protein Complex, full map | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.04 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Half map: Mu Opioid Receptor-Gi Protein Complex, half map #1
File | emd_7869_half_map_1.map | ||||||||||||
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Annotation | Mu Opioid Receptor-Gi Protein Complex, half map #1 | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Mu Opioid Receptor-Gi Protein Complex, half map #2
File | emd_7869_half_map_2.map | ||||||||||||
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Annotation | Mu Opioid Receptor-Gi Protein Complex, half map #2 | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
-Entire : Ternary complex of DAMGO-activated Mu-type opioid receptor with h...
Entire | Name: Ternary complex of DAMGO-activated Mu-type opioid receptor with heterotrimeric Gi |
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Components |
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-Supramolecule #1: Ternary complex of DAMGO-activated Mu-type opioid receptor with h...
Supramolecule | Name: Ternary complex of DAMGO-activated Mu-type opioid receptor with heterotrimeric Gi type: complex / ID: 1 / Parent: 0 / Macromolecule list: all Details: Signaling complex formed by incubation of DAMGO-bound Mu-type opioid receptor and heterotrimeric Gi. Excess GDP removed by addition of apyrase. |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 120 KDa |
-Macromolecule #1: 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: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 40.415031 KDa |
Recombinant expression | Organism: Trichoplusia ni (cabbage looper) |
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 FDVGGQRSER KKWIHCFEGV TAIIFCVALS DYDLVLAEDE EM NRMHESM KLFDSICNNK WFTDTSIILF LNKKDLFEEK IKKSPLTICY PEYAGSNTYE EAAAYIQCQF EDLNKRKDTK EIY THFTCA TDTKNVQFVF DAVTDVIIKN NLKDCGLF UniProtKB: Guanine nucleotide-binding protein G(i) subunit alpha-1 |
-Macromolecule #2: 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: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 37.671102 KDa |
Recombinant expression | Organism: Trichoplusia ni (cabbage looper) |
Sequence | String: PGSSGSELDQ LRQEAEQLKN QIRDARKACA DATLSQITNN IDPVGRIQMR TRRTLRGHLA KIYAMHWGTD SRLLVSASQD GKLIIWDSY TTNKVHAIPL RSSWVMTCAY APSGNYVACG GLDNICSIYN LKTREGNVRV SRELAGHTGY LSCCRFLDDN Q IVTSSGDT ...String: PGSSGSELDQ LRQEAEQLKN QIRDARKACA DATLSQITNN IDPVGRIQMR TRRTLRGHLA KIYAMHWGTD SRLLVSASQD GKLIIWDSY TTNKVHAIPL RSSWVMTCAY APSGNYVACG GLDNICSIYN LKTREGNVRV SRELAGHTGY LSCCRFLDDN Q IVTSSGDT TCALWDIETG QQTTTFTGHT GDVMSLSLAP DTRLFVSGAC DASAKLWDVR EGMCRQTFTG HESDINAICF FP NGNAFAT GSDDATCRLF DLRADQELMT YSHDNIICGI TSVSFSKSGR LLLAGYDDFN CNVWDALKAD RAGVLAGHDN RVS CLGVTD DGMAVATGSW DSFLKIWN UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 |
-Macromolecule #3: 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: 3 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 7.861143 KDa |
Recombinant expression | Organism: Trichoplusia ni (cabbage looper) |
Sequence | String: MASNNTASIA QARKLVEQLK MEANIDRIKV SKAAADLMAY CEAHAKEDPL LTPVPASENP FREKKFFCAI L UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 |
-Macromolecule #4: Mu-type opioid receptor
Macromolecule | Name: Mu-type opioid receptor / type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Mus musculus (house mouse) |
Molecular weight | Theoretical: 39.995105 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
Sequence | String: NISDCSDPLA PASCSPAPGS WLNLSHVDGN QSDPCGPNRT GLGENLYFQG SHSLCPQTGS PSMVTAITIM ALYSIVCVVG LFGNFLVMY VIVRYTKMKT ATNIYIFNLA LADALATSTL PFQSVNYLMG TWPFGNILCK IVISIDYYNM FTSIFTLCTM S VDRYIAVC ...String: NISDCSDPLA PASCSPAPGS WLNLSHVDGN QSDPCGPNRT GLGENLYFQG SHSLCPQTGS PSMVTAITIM ALYSIVCVVG LFGNFLVMY VIVRYTKMKT ATNIYIFNLA LADALATSTL PFQSVNYLMG TWPFGNILCK IVISIDYYNM FTSIFTLCTM S VDRYIAVC HPVKALDFRT PRNAKIVNVC NWILSSAIGL PVMFMATTKY RQGSIDCTLT FSHPTWYWEN LLKICVFIFA FI MPVLIIT VCYGLMILRL KSVRMLSGSK EKDRNLRRIT RMVLVVVAVF IVCWTPIHIY VIIKALITIP ETTFQTVSWH FCI ALGYTN SCLNPVLYAF LDENFKRCFR EFCIPTSSTI UniProtKB: Mu-type opioid receptor |
-Macromolecule #5: DAMGO
Macromolecule | Name: DAMGO / type: protein_or_peptide / ID: 5 / Details: analogue of enkephalin / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 513.587 Da |
Sequence | String: Y(DAL)G(MEA)(ETA) |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 7 mg/mL | ||||||||||||||||||||||||
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Buffer | pH: 7.5 Component:
Details: Solutions were made fresh. After buffer reconstitution, all buffers were filtered with 0.22um filter. | ||||||||||||||||||||||||
Grid | Model: Quantifoil R1.2/1.3 / Material: GOLD / Mesh: 200 / Support film - Material: CARBON / Support film - topology: HOLEY / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Time: 60 sec. / Pretreatment - Atmosphere: AIR / Pretreatment - Pressure: 0.039 kPa | ||||||||||||||||||||||||
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 293 K / Instrument: FEI VITROBOT MARK IV / Details: blot 1 second before plunging. | ||||||||||||||||||||||||
Details | This sample was monodisperse by negative stain and Cryo-EM analysis. |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: COUNTING / Number real images: 2642 / Average exposure time: 8.0 sec. / Average electron dose: 37.0 e/Å2 Details: Images were collected in movie-mode at 10 frames per second. |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Calibrated magnification: 48076 / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus min: 0.8 µm |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |