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- EMDB-30393: Cryo-EM structure of A77636 bound dopamine receptor DRD1-Gs signa... -
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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-30393 | |||||||||
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Title | Cryo-EM structure of A77636 bound dopamine receptor DRD1-Gs signaling complex | |||||||||
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Function / homology | ![]() dopamine neurotransmitter receptor activity / cerebral cortex GABAergic interneuron migration / Dopamine receptors / operant conditioning / dopamine binding / dopamine neurotransmitter receptor activity, coupled via Gs / regulation of dopamine uptake involved in synaptic transmission / modification of postsynaptic structure / heterotrimeric G-protein binding / regulation of dopamine metabolic process ...dopamine neurotransmitter receptor activity / cerebral cortex GABAergic interneuron migration / Dopamine receptors / operant conditioning / dopamine binding / dopamine neurotransmitter receptor activity, coupled via Gs / regulation of dopamine uptake involved in synaptic transmission / modification of postsynaptic structure / heterotrimeric G-protein binding / regulation of dopamine metabolic process / sensitization / dopamine transport / peristalsis / phospholipase C-activating dopamine receptor signaling pathway / G protein-coupled receptor complex / grooming behavior / positive regulation of neuron migration / habituation / astrocyte development / conditioned taste aversion / positive regulation of potassium ion transport / striatum development / dentate gyrus development / maternal behavior / arrestin family protein binding / non-motile cilium / adult walking behavior / mating behavior / long-term synaptic depression / ciliary membrane / G protein-coupled dopamine receptor signaling pathway / temperature homeostasis / dopamine metabolic process / transmission of nerve impulse / glucose import / PKA activation in glucagon signalling / G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / behavioral response to cocaine / hair follicle placode formation / mu-type opioid receptor binding / developmental growth / corticotropin-releasing hormone receptor 1 binding / G-protein alpha-subunit binding / intracellular transport / neuronal action potential / GABA-ergic synapse / D1 dopamine receptor binding / behavioral fear response / Hedgehog 'off' state / prepulse inhibition / beta-2 adrenergic receptor binding / adenylate cyclase-activating adrenergic receptor signaling pathway / synapse assembly / response to amphetamine / activation of adenylate cyclase activity / adenylate cyclase activator activity / presynaptic modulation of chemical synaptic transmission / positive regulation of synaptic transmission, glutamatergic / positive regulation of release of sequestered calcium ion into cytosol / trans-Golgi network membrane / synaptic transmission, glutamatergic / G protein-coupled receptor activity / long-term synaptic potentiation / regulation of protein phosphorylation / insulin-like growth factor receptor binding / ionotropic glutamate receptor binding / G-protein beta/gamma-subunit complex binding / Olfactory Signaling Pathway / Activation of the phototransduction cascade / visual learning / bone development / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / G-protein activation / G protein-coupled acetylcholine receptor signaling pathway / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / adenylate cyclase-activating G protein-coupled receptor signaling pathway / Prostacyclin signalling through prostacyclin receptor / Glucagon signaling in metabolic regulation / G beta:gamma signalling through CDC42 / ADP signalling through P2Y purinoceptor 12 / G beta:gamma signalling through BTK / memory / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / Sensory perception of sweet, bitter, and umami (glutamate) taste / cilium / cognition / photoreceptor disc membrane / Adrenaline,noradrenaline inhibits insulin secretion / Glucagon-type ligand receptors / Vasopressin regulates renal water homeostasis via Aquaporins / platelet aggregation / G alpha (z) signalling events / cellular response to catecholamine stimulus / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / ADORA2B mediated anti-inflammatory cytokines production / sensory perception of taste / ADP signalling through P2Y purinoceptor 1 Similarity search - Function | |||||||||
Biological species | ![]() ![]() ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.54 Å | |||||||||
![]() | Yan W / Shao Z | |||||||||
![]() | ![]() Title: Ligand recognition and allosteric regulation of DRD1-Gs signaling complexes. Authors: Peng Xiao / Wei Yan / Lu Gou / Ya-Ni Zhong / Liangliang Kong / Chao Wu / Xin Wen / Yuan Yuan / Sheng Cao / Changxiu Qu / Xin Yang / Chuan-Cheng Yang / Anjie Xia / Zhenquan Hu / Qianqian ...Authors: Peng Xiao / Wei Yan / Lu Gou / Ya-Ni Zhong / Liangliang Kong / Chao Wu / Xin Wen / Yuan Yuan / Sheng Cao / Changxiu Qu / Xin Yang / Chuan-Cheng Yang / Anjie Xia / Zhenquan Hu / Qianqian Zhang / Yong-Hao He / Dao-Lai Zhang / Chao Zhang / Gui-Hua Hou / Huanxiang Liu / Lizhe Zhu / Ping Fu / Shengyong Yang / Daniel M Rosenbaum / Jin-Peng Sun / Yang Du / Lei Zhang / Xiao Yu / Zhenhua Shao / ![]() ![]() Abstract: Dopamine receptors, including D1- and D2-like receptors, are important therapeutic targets in a variety of neurological syndromes, as well as cardiovascular and kidney diseases. Here, we present five ...Dopamine receptors, including D1- and D2-like receptors, are important therapeutic targets in a variety of neurological syndromes, as well as cardiovascular and kidney diseases. Here, we present five cryoelectron microscopy (cryo-EM) structures of the dopamine D1 receptor (DRD1) coupled to Gs heterotrimer in complex with three catechol-based agonists, a non-catechol agonist, and a positive allosteric modulator for endogenous dopamine. These structures revealed that a polar interaction network is essential for catecholamine-like agonist recognition, whereas specific motifs in the extended binding pocket were responsible for discriminating D1- from D2-like receptors. Moreover, allosteric binding at a distinct inner surface pocket improved the activity of DRD1 by stabilizing endogenous dopamine interaction at the orthosteric site. DRD1-Gs interface revealed key features that serve as determinants for G protein coupling. Together, our study provides a structural understanding of the ligand recognition, allosteric regulation, and G protein coupling mechanisms of DRD1. | |||||||||
History |
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Structure visualization
Movie |
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Structure viewer | EM map: ![]() ![]() ![]() |
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 36 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 18.3 KB 18.3 KB | Display Display | ![]() |
Images | ![]() | 63.2 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 447.4 KB | Display | ![]() |
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Full document | ![]() | 447 KB | Display | |
Data in XML | ![]() | 5.1 KB | Display | |
Data in CIF | ![]() | 5.8 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7ckxMC ![]() 7ckwC ![]() 7ckyC ![]() 7ckzC ![]() 7crhC M: atomic model generated by this map C: citing same article ( |
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Similar structure data |
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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 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
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Sample components
+Entire : EM structure of protein-2
+Supramolecule #1: EM structure of protein-2
+Supramolecule #2: Guanine nucleotide-binding protein G(s) subunit alpha, beta, gamma
+Supramolecule #3: Nanobody 35
+Supramolecule #4: D(1A) dopamine receptor
+Macromolecule #1: Guanine nucleotide-binding protein G(s) subunit alpha isoforms short
+Macromolecule #2: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
+Macromolecule #3: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
+Macromolecule #4: Nanobody 35
+Macromolecule #5: D(1A) dopamine receptor
+Macromolecule #6: (1R,3S)-3-(1-adamantyl)-1-(aminomethyl)-3,4-dihydro-1H-isochromen...
+Macromolecule #7: CHOLESTEROL
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Buffer | pH: 7.4 |
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Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277.15 K / Instrument: FEI VITROBOT MARK IV |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Average electron dose: 64.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: OTHER / Imaging mode: OTHER |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.54 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 391771 |
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Initial angle assignment | Type: OTHER |
Final angle assignment | Type: OTHER |