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Yorodumi- EMDB-21245: Structure of a D2 dopamine receptor-G-protein complex in a lipid ... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-21245 | |||||||||
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Title | Structure of a D2 dopamine receptor-G-protein complex in a lipid membrane | |||||||||
Map data | Catecholamine receptor structure | |||||||||
Sample |
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Biological species | Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.7 Å | |||||||||
Authors | Yin J / Chen KM / Clark MJ / Hijazi M / Kumari P / Bai X / Sunahara RK / Barth P / Rosenbaum DM | |||||||||
Funding support | United States, 1 items
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Citation | Journal: Nature / Year: 2020 Title: Structure of a D2 dopamine receptor-G-protein complex in a lipid membrane. Authors: Jie Yin / Kuang-Yui M Chen / Mary J Clark / Mahdi Hijazi / Punita Kumari / Xiao-Chen Bai / Roger K Sunahara / Patrick Barth / Daniel M Rosenbaum / Abstract: The D2 dopamine receptor (DRD2) is a therapeutic target for Parkinson's disease and antipsychotic drugs. DRD2 is activated by the endogenous neurotransmitter dopamine and synthetic agonist drugs such ...The D2 dopamine receptor (DRD2) is a therapeutic target for Parkinson's disease and antipsychotic drugs. DRD2 is activated by the endogenous neurotransmitter dopamine and synthetic agonist drugs such as bromocriptine, leading to stimulation of G and inhibition of adenylyl cyclase. Here we used cryo-electron microscopy to elucidate the structure of an agonist-bound activated DRD2-G complex reconstituted into a phospholipid membrane. The extracellular ligand-binding site of DRD2 is remodelled in response to agonist binding, with conformational changes in extracellular loop 2, transmembrane domain 5 (TM5), TM6 and TM7, propagating to opening of the intracellular G-binding site. The DRD2-G structure represents, to our knowledge, the first experimental model of a G-protein-coupled receptor-G-protein complex embedded in a phospholipid bilayer, which serves as a benchmark to validate the interactions seen in previous detergent-bound structures. The structure also reveals interactions that are unique to the membrane-embedded complex, including helix 8 burial in the inner leaflet, ordered lysine and arginine side chains in the membrane interfacial regions, and lipid anchoring of the G protein in the membrane. Our model of the activated DRD2 will help to inform the design of subtype-selective DRD2 ligands for multiple human central nervous system disorders. | |||||||||
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_21245.map.gz | 78.2 MB | EMDB map data format | |
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Header (meta data) | emd-21245-v30.xml emd-21245.xml | 10.6 KB 10.6 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_21245_fsc.xml | 10 KB | Display | FSC data file |
Images | emd_21245.png | 21.9 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-21245 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-21245 | HTTPS FTP |
-Validation report
Summary document | emd_21245_validation.pdf.gz | 79.5 KB | Display | EMDB validaton report |
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Full document | emd_21245_full_validation.pdf.gz | 78.6 KB | Display | |
Data in XML | emd_21245_validation.xml.gz | 494 B | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-21245 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-21245 | HTTPS FTP |
-Related structure data
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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-Map
File | Download / File: emd_21245.map.gz / Format: CCP4 / Size: 83.7 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | Catecholamine receptor structure | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 0.83 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Sample components
-Entire : D2 dopamine receptor-G protein complex
Entire | Name: D2 dopamine receptor-G protein complex |
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Components |
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-Supramolecule #1: D2 dopamine receptor-G protein complex
Supramolecule | Name: D2 dopamine receptor-G protein complex / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#5 |
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Source (natural) | Organism: Homo sapiens (human) |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.4 |
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Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 64.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
+Image processing
-Atomic model buiding 1
Initial model | PDB ID: |
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