+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-43732 | |||||||||
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Title | momSalB bound Kappa Opioid Receptor in complex Gi1 | |||||||||
Map data | A locally-refined map for Kappa-opioid receptor region | |||||||||
Sample |
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Keywords | GPCR / KAPPA OPIOID Receptor / SALVINORIN / MEMBRANE PROTEIN | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.71 Å | |||||||||
Authors | Fay JF / Che T | |||||||||
Funding support | United States, 1 items
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Citation | Journal: Nature / Year: 2023 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 | emd_43732.map.gz | 85 MB | EMDB map data format | |
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Header (meta data) | emd-43732-v30.xml emd-43732.xml | 13.9 KB 13.9 KB | Display Display | EMDB header |
Images | emd_43732.png | 25.9 KB | ||
Filedesc metadata | emd-43732.cif.gz | 4.8 KB | ||
Others | emd_43732_half_map_1.map.gz emd_43732_half_map_2.map.gz | 84.6 MB 84.6 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-43732 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-43732 | HTTPS FTP |
-Related structure data
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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-Map
File | Download / File: emd_43732.map.gz / Format: CCP4 / Size: 91.1 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Annotation | A locally-refined map for Kappa-opioid receptor region | ||||||||||||||||||||
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
-Half map: half map for the locally-refined map of Kappa-opioid receptor region
File | emd_43732_half_map_1.map | ||||||||||||
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Annotation | half map for the locally-refined map of Kappa-opioid receptor region | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: half map for the locally-refined map of Kappa-opioid receptor region
File | emd_43732_half_map_2.map | ||||||||||||
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Annotation | half map for the locally-refined map of Kappa-opioid receptor region | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
-Entire : momSalB bound Kappa Opioid Receptor in complex with Gi1
Entire | Name: momSalB bound Kappa Opioid Receptor in complex with Gi1 |
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Components |
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-Supramolecule #1: momSalB bound Kappa Opioid Receptor in complex with Gi1
Supramolecule | Name: momSalB bound Kappa Opioid Receptor in complex with Gi1 type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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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 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
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 |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.5 |
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Vitrification | Cryogen name: ETHANE-PROPANE |
-Electron microscopy
Microscope | FEI TALOS ARCTICA |
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Electron beam | Acceleration voltage: 200 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy / Nominal defocus max: 2.2 µm / Nominal defocus min: 0.4 µm |
Image recording | Film or detector model: GATAN K3 (6k x 4k) / Number real images: 4175 / Average electron dose: 47.4 e/Å2 |
Experimental equipment | Model: Talos Arctica / Image courtesy: FEI Company |
-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: 2.71 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 370551 |