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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 gustducin | |||||||||
![]() | deep sharp | |||||||||
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Function / homology | ![]() dynorphin receptor activity / response to acrylamide / regulation of saliva secretion / negative regulation of luteinizing hormone secretion / sensory perception of temperature stimulus / positive regulation of eating behavior / adenylate cyclase-inhibiting opioid receptor signaling pathway / G protein-coupled opioid receptor activity / G protein-coupled opioid receptor signaling pathway / ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() Similarity search - Function | |||||||||
Biological species | ![]() ![]() ![]() ![]() ![]() | |||||||||
Method | ![]() ![]() | |||||||||
![]() | 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. | |||||||||
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Structure visualization
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Downloads & links
-EMDB archive
Map data | ![]() | 78.3 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 21.8 KB 21.8 KB | Display Display | ![]() |
Images | ![]() | 41.2 KB | ||
Others | ![]() ![]() ![]() | 85.2 MB 84.6 MB 84.6 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8dzrMC ![]() 8dzpC ![]() 8dzqC ![]() 8dzsC 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_27806_additional_1.map | ||||||||||||
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Annotation | bfact sharp | ||||||||||||
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Density Histograms |
-Half map: half B
File | emd_27806_half_map_1.map | ||||||||||||
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Annotation | half B | ||||||||||||
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Density Histograms |
-Half map: half A
File | emd_27806_half_map_2.map | ||||||||||||
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Annotation | half A | ||||||||||||
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Density Histograms |
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Sample components
-Entire : GR89,696 bound Kappa Opioid Receptor in complex with gustducin
Entire | Name: GR89,696 bound Kappa Opioid Receptor in complex with gustducin |
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Components |
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-Supramolecule #1: GR89,696 bound Kappa Opioid Receptor in complex with gustducin
Supramolecule | Name: GR89,696 bound Kappa Opioid Receptor in complex with gustducin type: complex / ID: 1 / 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: 32.289387 KDa |
Recombinant expression | Organism: ![]() ![]() ![]() |
Sequence | String: GSISPAIPVI ITAVYSVVFV VGLVGNSLVM FVIIRYTKMK TATNIYIFNL ALADALVTTT MPFQSTVYLM NSWPFGDVLC KIVLSIDYY NMFTSIFTLT MMSVDRYIAV CHPVKALDFR TPLKAKIINI CIWLLSSSVG ISAIVLGGTK VREDVDVIEC S LQFPDDDY ...String: GSISPAIPVI ITAVYSVVFV VGLVGNSLVM FVIIRYTKMK TATNIYIFNL ALADALVTTT MPFQSTVYLM NSWPFGDVLC KIVLSIDYY NMFTSIFTLT MMSVDRYIAV CHPVKALDFR TPLKAKIINI CIWLLSSSVG ISAIVLGGTK VREDVDVIEC S LQFPDDDY SWWDLFMKIC VFIFAFVIPV LIIIVCYTLM ILRLKSVRLL SGSREKDRNL RRITRLVLVV VAVFVVCWTP IH IFILVEA LGSTSHSTAA LSSYYFCIAL GYTNSSLNPI LYAFLDENFK |
-Macromolecule #2: G alpha gustducin protein
Macromolecule | Name: G alpha gustducin protein / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 40.340898 KDa |
Recombinant expression | Organism: ![]() ![]() ![]() |
Sequence | String: MGSTVSAEDK AAAERSKMID KNLREDAERD ARTVKLLLLG AGESGKATIV KQMKIIHKNG YSEQECMEFK AVIYSNTLQS ILAIVKAMT TLGIDYVNPR SAEDQRQLYA MANTLEDGGM TPQLAEVIKR LWRDPGIQAC FERASEYQLN DSAAYYLNDL D RITASGYV ...String: MGSTVSAEDK AAAERSKMID KNLREDAERD ARTVKLLLLG AGESGKATIV KQMKIIHKNG YSEQECMEFK AVIYSNTLQS ILAIVKAMT TLGIDYVNPR SAEDQRQLYA MANTLEDGGM TPQLAEVIKR LWRDPGIQAC FERASEYQLN DSAAYYLNDL D RITASGYV PNEQDVLHSR VKTTGIIETQ FSFKDLHFRM FDVGAQRSER KKWIHCFEGV TCIIFCAALS AYDMVLVEDE EV NRMHASL KLFDSICNHK YFSDTSIVLF LNKKDIFQEK VTKVHLSICF PEYTGPNTFE DAGNYIKNQF LDLNLKKEDK EIY SHMTCS TDTQNVKFVF DAVTDIIIKE NLKDCGLF |
-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 | ![]() |
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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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Electron beam | Acceleration voltage: 200 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD![]() |
Image recording | Film or detector model: GATAN K3 (6k x 4k) / Number real images: 5752 / Average electron dose: 29.07 e/Å2 |
Experimental equipment | ![]() Model: Talos Arctica / Image courtesy: FEI Company |
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Image processing
Startup model | Type of model: NONE |
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Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 2.61 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 725271 |