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Open data
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Basic information
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Title | GR89,696 bound Kappa Opioid Receptor in complex with Gz | |||||||||
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Function / homology | ![]() adenylate cyclase inhibitor activity / dynorphin receptor activity / response to acrylamide / regulation of saliva secretion / sensory perception of temperature stimulus / positive regulation of eating behavior / G protein-coupled serotonin receptor signaling pathway / adenylate cyclase-inhibiting opioid receptor signaling pathway / G protein-coupled opioid receptor activity / negative regulation of luteinizing hormone secretion ...adenylate cyclase inhibitor activity / dynorphin receptor activity / response to acrylamide / regulation of saliva secretion / sensory perception of temperature stimulus / positive regulation of eating behavior / G protein-coupled serotonin receptor signaling pathway / adenylate cyclase-inhibiting opioid receptor signaling pathway / G protein-coupled opioid receptor activity / negative regulation of luteinizing hormone secretion / G protein-coupled opioid receptor signaling pathway / positive regulation of dopamine secretion / sensory perception / positive regulation of potassium ion transmembrane transport / conditioned place preference / maternal behavior / receptor serine/threonine kinase binding / neuropeptide binding / positive regulation of p38MAPK cascade / eating behavior / behavioral response to cocaine / estrous cycle / neuropeptide signaling pathway / negative regulation of insulin secretion / G protein-coupled serotonin receptor binding / MECP2 regulates neuronal receptors and channels / axon terminus / sensory perception of pain / T-tubule / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / Peptide ligand-binding receptors / sarcoplasmic reticulum / locomotory behavior / G protein-coupled receptor binding / cellular response to glucose stimulus / response to nicotine / G-protein beta/gamma-subunit complex binding / Olfactory Signaling Pathway / Activation of the phototransduction cascade / response to insulin / 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 activation / G protein-coupled acetylcholine receptor signaling pathway / 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 / G beta:gamma signalling through CDC42 / ADP signalling through P2Y purinoceptor 12 / G beta:gamma signalling through BTK / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / Sensory perception of sweet, bitter, and umami (glutamate) taste / synaptic vesicle membrane / photoreceptor disc membrane / Adrenaline,noradrenaline inhibits insulin secretion / Glucagon-type ligand receptors / Vasopressin regulates renal water homeostasis via Aquaporins / G alpha (z) signalling events / cellular response to catecholamine stimulus / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / ADORA2B mediated anti-inflammatory cytokines production / sensory perception of taste / response to estrogen / ADP signalling through P2Y purinoceptor 1 / adenylate cyclase-activating dopamine receptor signaling pathway / G beta:gamma signalling through PI3Kgamma / cellular response to prostaglandin E stimulus / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / GPER1 signaling / G-protein beta-subunit binding / Inactivation, recovery and regulation of the phototransduction cascade / 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 / nuclear envelope / presynaptic membrane / phospholipase C-activating G protein-coupled receptor signaling pathway / Ca2+ pathway / G alpha (i) signalling events / cell body / fibroblast proliferation / G alpha (s) signalling events / G alpha (q) signalling events / chemical synaptic transmission / cellular response to lipopolysaccharide / postsynaptic membrane / perikaryon / response to ethanol / defense response to virus / cell population proliferation / Ras protein signal transduction / Extra-nuclear estrogen signaling / neuron projection Similarity search - Function | |||||||||
Biological species | ![]() ![]() ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.65 Å | |||||||||
![]() | Fay JF / Che T | |||||||||
Funding support | ![]()
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![]() | ![]() Title: Ligand and G-protein selectivity in the κ-opioid receptor. Authors: Jianming Han / Jingying Zhang / Antonina L Nazarova / Sarah M Bernhard / Brian E Krumm / Lei Zhao / Jordy Homing Lam / Vipin A Rangari / Susruta Majumdar / David E Nichols / Vsevolod ...Authors: Jianming Han / Jingying Zhang / Antonina L Nazarova / Sarah M Bernhard / Brian E Krumm / Lei Zhao / Jordy Homing Lam / Vipin A Rangari / Susruta Majumdar / David E Nichols / Vsevolod Katritch / Peng Yuan / Jonathan F Fay / Tao Che / ![]() Abstract: The κ-opioid receptor (KOR) represents a highly desirable therapeutic target for treating not only pain but also addiction and affective disorders. However, the development of KOR analgesics has ...The κ-opioid receptor (KOR) represents a highly desirable therapeutic target for treating not only pain but also addiction and affective disorders. However, the development of KOR analgesics has been hindered by the associated hallucinogenic side effects. The initiation of KOR signalling requires the G-family proteins including the conventional (G, G, G, G and G) and nonconventional (G and G) subtypes. How hallucinogens exert their actions through KOR and how KOR determines G-protein subtype selectivity are not well understood. Here we determined the active-state structures of KOR in a complex with multiple G-protein heterotrimers-G, G, G and G-using cryo-electron microscopy. The KOR-G-protein complexes are bound to hallucinogenic salvinorins or highly selective KOR agonists. Comparisons of these structures reveal molecular determinants critical for KOR-G-protein interactions as well as key elements governing G-family subtype selectivity and KOR ligand selectivity. Furthermore, the four G-protein subtypes display an intrinsically different binding affinity and allosteric activity on agonist binding at KOR. These results provide insights into the actions of opioids and G-protein-coupling specificity at KOR and establish a foundation to examine the therapeutic potential of pathway-selective agonists of KOR. | |||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 77.1 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 21.7 KB 21.7 KB | Display Display | ![]() |
Images | ![]() | 41.2 KB | ||
Others | ![]() ![]() ![]() | 85.2 MB 84.5 MB 84.5 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 745.7 KB | Display | ![]() |
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Full document | ![]() | 745.2 KB | Display | |
Data in XML | ![]() | 12.9 KB | Display | |
Data in CIF | ![]() | 15.1 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8dzsMC ![]() 8dzpC ![]() 8dzqC ![]() 8dzrC C: citing same article ( M: atomic model generated by this map |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Annotation | deep sharp | ||||||||||||||||||||
Voxel size | X=Y=Z: 0.88 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Additional map: Bfact sharp
File | emd_27807_additional_1.map | ||||||||||||
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Annotation | Bfact sharp | ||||||||||||
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Density Histograms |
-Half map: half A
File | emd_27807_half_map_1.map | ||||||||||||
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Annotation | half A | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: half B
File | emd_27807_half_map_2.map | ||||||||||||
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Annotation | half B | ||||||||||||
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Density Histograms |
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Sample components
-Entire : GR89,696 bound Kappa Opioid Receptor in complex with Gz
Entire | Name: GR89,696 bound Kappa Opioid Receptor in complex with Gz |
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Components |
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-Supramolecule #1: GR89,696 bound Kappa Opioid Receptor in complex with Gz
Supramolecule | Name: GR89,696 bound Kappa Opioid Receptor in complex with Gz type: complex / ID: 1 / Chimera: Yes / Parent: 0 / Macromolecule list: #1-#5 |
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Source (natural) | Organism: ![]() |
-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: ![]() |
Molecular weight | Theoretical: 34.928555 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: LGSISPAIPV IITAVYSVVF VVGLVGNSLV MFVIIRYTKM KTATNIYIFN LALADALVTT TMPFQSTVYL MNSWPFGDVL CKIVLSIDY YNMFTSIFTL TMMSVDRYIA VCHPVKALDF RTPLKAKIIN ICIWLLSSSV GISAIVLGGT KVREDVDVIE C SLQFPDDD ...String: LGSISPAIPV IITAVYSVVF VVGLVGNSLV MFVIIRYTKM KTATNIYIFN LALADALVTT TMPFQSTVYL MNSWPFGDVL CKIVLSIDY YNMFTSIFTL TMMSVDRYIA VCHPVKALDF RTPLKAKIIN ICIWLLSSSV GISAIVLGGT KVREDVDVIE C SLQFPDDD YSWWDLFMKI CVFIFAFVIP VLIIIVCYTL MILRLKSVRL LSGSREKDRN LRRITRLVLV VVAVFVVCWT PI HIFILVE ALGSTSHSTA ALSSYYFCIA LGYTNSSLNP ILYAFLDENF KRCFRDFCFP LKMRMERQST S |
-Macromolecule #2: Guanine nucleotide-binding protein G(z) subunit alpha
Macromolecule | Name: Guanine nucleotide-binding protein G(z) subunit alpha / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 39.849551 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: MGSTVSAEDK AAAERSKMID KNLREDGEKQ RREIKLLLLG TSNSGKNTIV KQMKIIHSGG FNLEACKEYK PLIIYNAIDS LTRIIRALA ALRIDFHNPD RAYDAVQLFA LTGPAESKGE ITPELLGVMR RLWADPGAQA CFSRSSEYHL EDNAAYYLND L ERIAAADY ...String: MGSTVSAEDK AAAERSKMID KNLREDGEKQ RREIKLLLLG TSNSGKNTIV KQMKIIHSGG FNLEACKEYK PLIIYNAIDS LTRIIRALA ALRIDFHNPD RAYDAVQLFA LTGPAESKGE ITPELLGVMR RLWADPGAQA CFSRSSEYHL EDNAAYYLND L ERIAAADY IPTVEDILRS RDMTTGIVEN KFTFKELTFK MVDVGAQRSE RKKWIHCFEG VTAIIFCVEL SGYDLQTSRM AA SLKLFDS ICNNKWFIDT SLILFLNKKD LLAEKIRRIP LTICFPEYKG QNTYEEAAVY IQRQFEDLNR NKETKEIYSH FTC STDTSN IQFVFDAVTD VIIQNNLKYI GLC |
-Macromolecule #3: 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: 3 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 37.285734 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: SELDQLRQEA EQLKNQIRDA RKACADATLS QITNNIDPVG RIQMRTRRTL RGHLAKIYAM HWGTDSRLLV SASQDGKLII WDSYTTNKV HAIPLRSSWV MTCAYAPSGN YVACGGLDNI CSIYNLKTRE GNVRVSRELA GHTGYLSCCR FLDDNQIVTS S GDTTCALW ...String: SELDQLRQEA EQLKNQIRDA RKACADATLS QITNNIDPVG RIQMRTRRTL RGHLAKIYAM HWGTDSRLLV SASQDGKLII WDSYTTNKV HAIPLRSSWV MTCAYAPSGN YVACGGLDNI CSIYNLKTRE GNVRVSRELA GHTGYLSCCR FLDDNQIVTS S GDTTCALW DIETGQQTTT FTGHTGDVMS LSLAPDTRLF VSGACDASAK LWDVREGMCR QTFTGHESDI NAICFFPNGN AF ATGSDDA TCRLFDLRAD QELMTYSHDN IICGITSVSF SKSGRLLLAG YDDFNCNVWD ALKADRAGVL AGHDNRVSCL GVT DDGMAV ATGSWDSFLK IWN |
-Macromolecule #4: 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: 4 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 7.861143 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: MASNNTASIA QARKLVEQLK MEANIDRIKV SKAAADLMAY CEAHAKEDPL LTPVPASENP FREKKFFCAI L |
-Macromolecule #5: ScFv16 protein
Macromolecule | Name: ScFv16 protein / type: protein_or_peptide / ID: 5 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 26.679721 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: DVQLVESGGG LVQPGGSRKL SCSASGFAFS SFGMHWVRQA PEKGLEWVAY ISSGSGTIYY ADTVKGRFTI SRDDPKNTLF LQMTSLRSE DTAMYYCVRS IYYYGSSPFD FWGQGTTLTV SSGGGGSGGG GSGGGGSDIV MTQATSSVPV TPGESVSISC R SSKSLLHS ...String: DVQLVESGGG LVQPGGSRKL SCSASGFAFS SFGMHWVRQA PEKGLEWVAY ISSGSGTIYY ADTVKGRFTI SRDDPKNTLF LQMTSLRSE DTAMYYCVRS IYYYGSSPFD FWGQGTTLTV SSGGGGSGGG GSGGGGSDIV MTQATSSVPV TPGESVSISC R SSKSLLHS NGNTYLYWFL QRPGQSPQLL IYRMSNLASG VPDRFSGSGS GTAFTLTISR LEAEDVGVYY CMQHLEYPLT FG AGTKLEL KAAA |
-Macromolecule #6: methyl (3R)-4-[(3,4-dichlorophenyl)acetyl]-3-[(pyrrolidin-1-yl)me...
Macromolecule | Name: methyl (3R)-4-[(3,4-dichlorophenyl)acetyl]-3-[(pyrrolidin-1-yl)methyl]piperazine-1-carboxylate type: ligand / ID: 6 / Number of copies: 1 / Formula: U9I |
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Molecular weight | Theoretical: 414.326 Da |
Chemical component information | ![]() ChemComp-U9I: |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Buffer | pH: 7.5 |
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Vitrification | Cryogen name: ETHANE-PROPANE |
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Electron microscopy
Microscope | FEI TALOS ARCTICA |
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Image recording | Film or detector model: GATAN K3 (6k x 4k) / Number real images: 5752 / Average electron dose: 29.07 e/Å2 |
Electron beam | Acceleration voltage: 200 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.5 µm / Nominal defocus min: 0.1 µm |
Experimental equipment | ![]() Model: Talos Arctica / Image courtesy: FEI Company |
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Image processing
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 2.65 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 643193 |
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Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |