+
Open data
-
Basic information
Entry | ![]() | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Title | momSalB bound Kappa Opioid Receptor in complex with GoA | |||||||||
![]() | The locally-refined map of kappa-opioid receptor region | |||||||||
![]() |
| |||||||||
![]() | GPCR / Receptor / Kappa / KOR / Opioid / MEMBRANE PROTEIN | |||||||||
Biological species | ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.8 Å | |||||||||
![]() | Fay JF / Che T | |||||||||
Funding support | ![]()
| |||||||||
![]() | ![]() 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 |
|
-
Structure visualization
Supplemental images |
---|
-
Downloads & links
-EMDB archive
Map data | ![]() | 84.9 MB | ![]() | |
---|---|---|---|---|
Header (meta data) | ![]() ![]() | 14 KB 14 KB | Display Display | ![]() |
Images | ![]() | 46.9 KB | ||
Filedesc metadata | ![]() | 4.8 KB | ||
Others | ![]() ![]() | 84.4 MB 84.4 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 774.6 KB | Display | ![]() |
---|---|---|---|---|
Full document | ![]() | 774.2 KB | Display | |
Data in XML | ![]() | 12.8 KB | Display | |
Data in CIF | ![]() | 15 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
-
Links
EMDB pages | ![]() ![]() |
---|
-
Map
File | ![]() | ||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | The locally-refined map of kappa-opioid receptor region | ||||||||||||||||||||
Voxel size | X=Y=Z: 0.88 Å | ||||||||||||||||||||
Density |
| ||||||||||||||||||||
Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
|
-Supplemental data
-Half map: Half map of the locally-refined map of kappa-opioid receptor region
File | emd_41876_half_map_1.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | Half map of the locally-refined map of kappa-opioid receptor region | ||||||||||||
Projections & Slices |
| ||||||||||||
Density Histograms |
-Half map: Half map of the locally-refined map of kappa-opioid receptor region
File | emd_41876_half_map_2.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | Half map of the locally-refined map of kappa-opioid receptor region | ||||||||||||
Projections & Slices |
| ||||||||||||
Density Histograms |
-
Sample components
-Entire : momSalB bound Kappa Opioid Receptor in complex with GoA
Entire | Name: momSalB bound Kappa Opioid Receptor in complex with GoA |
---|---|
Components |
|
-Supramolecule #1: momSalB bound Kappa Opioid Receptor in complex with GoA
Supramolecule | Name: momSalB bound Kappa Opioid Receptor in complex with GoA type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
---|---|
Source (natural) | Organism: ![]() |
-Macromolecule #1: Kappa-type opioid receptor
Macromolecule | Name: Kappa-type opioid receptor / type: protein_or_peptide / ID: 1 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: ![]() |
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 |
-Experimental details
-Structure determination
Method | cryo EM |
---|---|
![]() | single particle reconstruction |
Aggregation state | particle |
-
Sample preparation
Buffer | pH: 7.5 |
---|---|
Vitrification | Cryogen name: ETHANE-PROPANE |
-
Electron microscopy
Microscope | FEI TALOS ARCTICA |
---|---|
Image recording | Film or detector model: GATAN K3 (6k x 4k) / Number real images: 3853 / Average electron dose: 42.7 e/Å2 |
Electron beam | Acceleration voltage: 200 kV / Electron source: ![]() |
Electron optics | C2 aperture diameter: 100.0 µm / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 2.7 µm / Nominal defocus min: 0.2 µm |
Experimental equipment | ![]() Model: Talos Arctica / Image courtesy: FEI Company |
-
Image processing
Startup model | Type of model: NONE |
---|---|
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 2.8 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 991076 |
Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |