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- PDB-7jvr: Cryo-EM structure of Bromocriptine-bound dopamine receptor 2 in c... -
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Open data
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Basic information
Entry | Database: PDB / ID: 7jvr | ||||||||||||||||||||||||||||||||||||
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Title | Cryo-EM structure of Bromocriptine-bound dopamine receptor 2 in complex with Gi protein | ||||||||||||||||||||||||||||||||||||
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![]() | SIGNALING PROTEIN / Dopamine receptor 2 / Gi protein / bromocriptine | ||||||||||||||||||||||||||||||||||||
Function / homology | ![]() negative regulation of dopamine receptor signaling pathway / positive regulation of dopamine uptake involved in synaptic transmission / negative regulation of dephosphorylation / negative regulation of circadian sleep/wake cycle, sleep / positive regulation of glial cell-derived neurotrophic factor production / acid secretion / dopamine neurotransmitter receptor activity, coupled via Gi/Go / nervous system process involved in regulation of systemic arterial blood pressure / regulation of synapse structural plasticity / response to histamine ...negative regulation of dopamine receptor signaling pathway / positive regulation of dopamine uptake involved in synaptic transmission / negative regulation of dephosphorylation / negative regulation of circadian sleep/wake cycle, sleep / positive regulation of glial cell-derived neurotrophic factor production / acid secretion / dopamine neurotransmitter receptor activity, coupled via Gi/Go / nervous system process involved in regulation of systemic arterial blood pressure / regulation of synapse structural plasticity / response to histamine / regulation of locomotion involved in locomotory behavior / neuron-neuron synaptic transmission / adenohypophysis development / positive regulation of renal sodium excretion / negative regulation of cellular response to hypoxia / positive regulation of growth hormone secretion / regulation of potassium ion transport / hyaloid vascular plexus regression / cerebral cortex GABAergic interneuron migration / negative regulation of dopamine secretion / adenylate cyclase-inhibiting dopamine receptor signaling pathway / response to inactivity / Dopamine receptors / orbitofrontal cortex development / negative regulation of neuron migration / regulation of dopamine uptake involved in synaptic transmission / branching morphogenesis of a nerve / dopamine binding / phospholipase C-activating dopamine receptor signaling pathway / heterotrimeric G-protein binding / peristalsis / drinking behavior / G protein-coupled receptor complex / grooming behavior / behavioral response to ethanol / auditory behavior / positive regulation of G protein-coupled receptor signaling pathway / striatum development / dopaminergic synapse / negative regulation of adenylate cyclase activity / positive regulation of urine volume / positive regulation of multicellular organism growth / G protein-coupled receptor internalization / negative regulation of synaptic transmission, glutamatergic / cellular response to ethanol / non-motile cilium / response to iron ion / adult walking behavior / response to morphine / ciliary membrane / arachidonate secretion / negative regulation of cytosolic calcium ion concentration / pigmentation / temperature homeostasis / heterocyclic compound binding / positive regulation of neuroblast proliferation / regulation of synaptic transmission, GABAergic / dopamine uptake involved in synaptic transmission / regulation of dopamine secretion / positive regulation of cytokinesis / dopamine metabolic process / associative learning / behavioral response to cocaine / positive regulation of receptor internalization / sperm flagellum / response to light stimulus / endocytic vesicle / neuroblast proliferation / G-protein alpha-subunit binding / response to axon injury / long-term memory / negative regulation of protein secretion / lateral plasma membrane / prepulse inhibition / postsynaptic modulation of chemical synaptic transmission / potassium channel regulator activity / negative regulation of insulin secretion / positive regulation of protein localization to cell cortex / Adenylate cyclase inhibitory pathway / T cell migration / regulation of sodium ion transport / synapse assembly / D2 dopamine receptor binding / cellular response to retinoic acid / ionotropic glutamate receptor binding / response to prostaglandin E / G protein-coupled serotonin receptor binding / adenylate cyclase regulator activity / adenylate cyclase-inhibiting serotonin receptor signaling pathway / negative regulation of blood pressure / axon terminus / release of sequestered calcium ion into cytosol / presynaptic modulation of chemical synaptic transmission / cellular response to forskolin / response to amphetamine / negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / regulation of mitotic spindle organization / axonogenesis / regulation of heart rate / negative regulation of innate immune response Similarity search - Function | ||||||||||||||||||||||||||||||||||||
Biological species | ![]() ![]() ![]() synthetic construct (others) | ||||||||||||||||||||||||||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.8 Å | ||||||||||||||||||||||||||||||||||||
![]() | Zhuang, Y. / Xu, P. / Mao, C. / Wang, L. / Krumm, B. / Zhou, X.E. / Huang, S. / Liu, H. / Cheng, X. / Huang, X.-P. ...Zhuang, Y. / Xu, P. / Mao, C. / Wang, L. / Krumm, B. / Zhou, X.E. / Huang, S. / Liu, H. / Cheng, X. / Huang, X.-P. / Sheng, D.-D. / Xu, T. / Liu, Y.-F. / Wang, Y. / Guo, J. / Jiang, Y. / Jiang, H. / Melcher, K. / Roth, B.L. / Zhang, Y. / Zhang, C. / Xu, H.E. | ||||||||||||||||||||||||||||||||||||
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![]() | ![]() Title: Structural insights into the human D1 and D2 dopamine receptor signaling complexes. Authors: Youwen Zhuang / Peiyu Xu / Chunyou Mao / Lei Wang / Brian Krumm / X Edward Zhou / Sijie Huang / Heng Liu / Xi Cheng / Xi-Ping Huang / Dan-Dan Shen / Tinghai Xu / Yong-Feng Liu / Yue Wang / ...Authors: Youwen Zhuang / Peiyu Xu / Chunyou Mao / Lei Wang / Brian Krumm / X Edward Zhou / Sijie Huang / Heng Liu / Xi Cheng / Xi-Ping Huang / Dan-Dan Shen / Tinghai Xu / Yong-Feng Liu / Yue Wang / Jia Guo / Yi Jiang / Hualiang Jiang / Karsten Melcher / Bryan L Roth / Yan Zhang / Cheng Zhang / H Eric Xu / ![]() ![]() Abstract: The D1- and D2-dopamine receptors (D1R and D2R), which signal through G and G, respectively, represent the principal stimulatory and inhibitory dopamine receptors in the central nervous system. D1R ...The D1- and D2-dopamine receptors (D1R and D2R), which signal through G and G, respectively, represent the principal stimulatory and inhibitory dopamine receptors in the central nervous system. D1R and D2R also represent the main therapeutic targets for Parkinson's disease, schizophrenia, and many other neuropsychiatric disorders, and insight into their signaling is essential for understanding both therapeutic and side effects of dopaminergic drugs. Here, we report four cryoelectron microscopy (cryo-EM) structures of D1R-G and D2R-G signaling complexes with selective and non-selective dopamine agonists, including two currently used anti-Parkinson's disease drugs, apomorphine and bromocriptine. These structures, together with mutagenesis studies, reveal the conserved binding mode of dopamine agonists, the unique pocket topology underlying ligand selectivity, the conformational changes in receptor activation, and potential structural determinants for G protein-coupling selectivity. These results provide both a molecular understanding of dopamine signaling and multiple structural templates for drug design targeting the dopaminergic system. | ||||||||||||||||||||||||||||||||||||
History |
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Structure visualization
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Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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PDBx/mmCIF format | ![]() | 245.5 KB | Display | ![]() |
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PDB format | ![]() | 184.4 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 22511MC ![]() 7jv5C ![]() 7jvpC ![]() 7jvqC M: map data used to model this data C: citing same article ( |
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Similar structure data |
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Links
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Assembly
Deposited unit | ![]()
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Components
-Guanine nucleotide-binding protein ... , 3 types, 3 molecules ABC
#2: Protein | Mass: 40414.047 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
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#3: Protein | Mass: 38146.707 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
#4: Protein | Mass: 7861.143 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
-Protein / Antibody / Non-polymers , 3 types, 3 molecules RE

#1: Protein | Mass: 67234.578 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() Gene: cybC, DRD2 / Production host: ![]() ![]() |
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#5: Antibody | Mass: 28813.047 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) synthetic construct (others) / Production host: ![]() ![]() |
#6: Chemical | ChemComp-08Y / |
-Details
Has ligand of interest | Y |
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Has protein modification | Y |
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
Component | Name: Bromocriptin-bound dopamine receptor 2 in complex with Gi protein Type: COMPLEX / Entity ID: #1-#5 / Source: RECOMBINANT |
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Source (natural) | Organism: ![]() |
Source (recombinant) | Organism: ![]() ![]() |
Buffer solution | pH: 7.2 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
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Electron microscopy imaging
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: ![]() |
Electron lens | Mode: BRIGHT FIELD |
Image recording | Electron dose: 64 e/Å2 / Film or detector model: GATAN K2 BASE (4k x 4k) |
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Processing
Software | Name: PHENIX / Version: 1.13_2998: / Classification: refinement |
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EM software | Name: PHENIX / Category: model refinement |
CTF correction | Type: NONE |
3D reconstruction | Resolution: 2.8 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 632558 / Symmetry type: POINT |