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- EMDB-32964: Cryo-EM structure of the fenoldopam-bound D1 dopamine receptor an... -
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Open data
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Basic information
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Title | Cryo-EM structure of the fenoldopam-bound D1 dopamine receptor and mini-Gs complex | |||||||||
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Function / homology | ![]() dopamine neurotransmitter receptor activity / cerebral cortex GABAergic interneuron migration / ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() Similarity search - Function | |||||||||
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Method | ![]() ![]() | |||||||||
![]() | Teng X / Zheng S | |||||||||
Funding support | ![]()
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![]() | ![]() Title: Ligand recognition and biased agonism of the D1 dopamine receptor. Authors: Xiao Teng / Sijia Chen / Yingying Nie / Peng Xiao / Xiao Yu / Zhenhua Shao / Sanduo Zheng / ![]() Abstract: Dopamine receptors are widely distributed in the central nervous system and are important therapeutic targets for treatment of various psychiatric and neurological diseases. Here, we report three ...Dopamine receptors are widely distributed in the central nervous system and are important therapeutic targets for treatment of various psychiatric and neurological diseases. Here, we report three cryo-electron microscopy structures of the D1 dopamine receptor (D1R)-Gs complex bound to two agonists, fenoldopam and tavapadon, and a positive allosteric modulator LY3154207. The structure reveals unusual binding of two fenoldopam molecules, one to the orthosteric binding pocket (OBP) and the other to the extended binding pocket (EBP). In contrast, one elongated tavapadon molecule binds to D1R, extending from OBP to EBP. Moreover, LY3154207 stabilizes the second intracellular loop of D1R in an alpha helical conformation to efficiently engage the G protein. Through a combination of biochemical, biophysical and cellular assays, we further show that the broad conformation stabilized by two fenoldopam molecules and interaction between TM5 and the agonist are important for biased signaling of D1R. | |||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 20.9 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 18.7 KB 18.7 KB | Display Display | ![]() |
Images | ![]() | 36.8 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7x2cMC ![]() 7x2dC ![]() 7x2fC M: atomic model generated by this map C: citing same article ( |
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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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Voxel size | X=Y=Z: 1.087 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
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Sample components
+Entire : Cryo-EM structure of the fenoldopam-bound D1R-miniGs complex
+Supramolecule #1: Cryo-EM structure of the fenoldopam-bound D1R-miniGs complex
+Supramolecule #2: the fenoldopam-bound D1R-miniGs
+Supramolecule #3: nanobody35
+Supramolecule #4: Gbeta-1gama-2
+Macromolecule #1: D(1A) dopamine receptor
+Macromolecule #2: Guanine nucleotide-binding protein G(s) subunit alpha isoforms sh...
+Macromolecule #3: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
+Macromolecule #4: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
+Macromolecule #5: Nanobody35
+Macromolecule #6: CHOLESTEROL
+Macromolecule #7: (1R)-6-chloranyl-1-(4-hydroxyphenyl)-2,3,4,5-tetrahydro-1H-3-benz...
-Experimental details
-Structure determination
Method | ![]() |
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Aggregation state | particle |
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Sample preparation
Concentration | 4.0 mg/mL |
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Buffer | pH: 7.5 |
Grid | Model: Quantifoil R1.2/1.3 / Material: GOLD / Mesh: 300 / Support film - Material: CARBON / Support film - topology: HOLEY / Pretreatment - Type: GLOW DISCHARGE |
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 281 K / Instrument: FEI VITROBOT MARK IV |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD![]() |
Sample stage | Cooling holder cryogen: NITROGEN |
Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Number real images: 1035 / Average electron dose: 50.0 e/Å2 |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
Particle selection | Number selected: 1791079 |
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CTF correction | Software - Name: cryoSPARC (ver. v3) Software - details: CTF parameters were estimated using patch-based CTF estimation |
Startup model | Type of model: EMDB MAP EMDB ID: |
Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final 3D classification | Number classes: 4 / Avg.num./class: 259 / Software - Name: cryoSPARC |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |
Final reconstruction | Number classes used: 1 / Resolution.type: BY AUTHOR / Resolution: 3.2 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 124932 |