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Yorodumi- PDB-7jvr: Cryo-EM structure of Bromocriptine-bound dopamine receptor 2 in c... -
+Open data
-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 | |||||||||||||||
Components |
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Keywords | SIGNALING PROTEIN / Dopamine receptor 2 / Gi protein / bromocriptine | |||||||||||||||
Function / homology | Function and homology information regulation of locomotion involved in locomotory behavior / negative regulation of dopamine receptor signaling pathway / positive regulation of dopamine uptake involved in synaptic transmission / negative regulation of circadian sleep/wake cycle, sleep / acid secretion / positive regulation of glial cell-derived neurotrophic factor production / dopamine neurotransmitter receptor activity, coupled via Gi/Go / nervous system process involved in regulation of systemic arterial blood pressure / auditory behavior / regulation of synapse structural plasticity ...regulation of locomotion involved in locomotory behavior / negative regulation of dopamine receptor signaling pathway / positive regulation of dopamine uptake involved in synaptic transmission / negative regulation of circadian sleep/wake cycle, sleep / acid secretion / positive regulation of glial cell-derived neurotrophic factor production / dopamine neurotransmitter receptor activity, coupled via Gi/Go / nervous system process involved in regulation of systemic arterial blood pressure / auditory behavior / regulation of synapse structural plasticity / response to histamine / positive regulation of renal sodium excretion / adenohypophysis development / neuron-neuron synaptic transmission / hyaloid vascular plexus regression / adenylate cyclase-inhibiting dopamine receptor signaling pathway / cerebral cortex GABAergic interneuron migration / negative regulation of neuron migration / response to inactivity / regulation of potassium ion transport / Dopamine receptors / orbitofrontal cortex development / dopamine binding / negative regulation of cellular response to hypoxia / regulation of dopamine uptake involved in synaptic transmission / branching morphogenesis of a nerve / negative regulation of voltage-gated calcium channel activity / negative regulation of dopamine secretion / positive regulation of growth hormone secretion / heterotrimeric G-protein binding / dopaminergic synapse / drinking behavior / grooming behavior / peristalsis / phospholipase C-activating dopamine receptor signaling pathway / G protein-coupled receptor complex / behavioral response to ethanol / positive regulation of G protein-coupled receptor signaling pathway / positive regulation of urine volume / striatum development / negative regulation of adenylate cyclase activity / negative regulation of synaptic transmission, glutamatergic / positive regulation of multicellular organism growth / response to morphine / non-motile cilium / G protein-coupled receptor internalization / adult walking behavior / response to iron ion / dopamine uptake involved in synaptic transmission / pigmentation / ciliary membrane / temperature homeostasis / regulation of synaptic transmission, GABAergic / arachidonic acid secretion / dopamine metabolic process / positive regulation of neuroblast proliferation / postsynaptic modulation of chemical synaptic transmission / regulation of dopamine secretion / heterocyclic compound binding / negative regulation of cytosolic calcium ion concentration / positive regulation of cytokinesis / behavioral response to cocaine / associative learning / positive regulation of receptor internalization / response to light stimulus / endocytic vesicle / neuroblast proliferation / Adenylate cyclase inhibitory pathway / negative regulation of protein secretion / negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / GABA-ergic synapse / positive regulation of protein localization to cell cortex / G-protein alpha-subunit binding / response to axon injury / potassium channel regulator activity / lateral plasma membrane / negative regulation of insulin secretion / regulation of cAMP-mediated signaling / long-term memory / sperm flagellum / D2 dopamine receptor binding / G protein-coupled serotonin receptor binding / prepulse inhibition / axon terminus / adenylate cyclase-activating adrenergic receptor signaling pathway / regulation of mitotic spindle organization / regulation of sodium ion transport / cellular response to forskolin / release of sequestered calcium ion into cytosol / synapse assembly / ionotropic glutamate receptor binding / response to amphetamine / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / excitatory postsynaptic potential / presynaptic modulation of chemical synaptic transmission / negative regulation of blood pressure / regulation of heart rate / negative regulation of innate immune response / axonogenesis / negative regulation of cell migration Similarity search - Function | |||||||||||||||
Biological species | Escherichia coli (E. coli) Homo sapiens (human) synthetic construct (others) | |||||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.8 Å | |||||||||||||||
Authors | 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. | |||||||||||||||
Funding support | China, United States, 4items
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Citation | Journal: Cell / Year: 2021 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
Movie |
Movie viewer |
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Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 7jvr.cif.gz | 238.9 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7jvr.ent.gz | 187.6 KB | Display | PDB format |
PDBx/mmJSON format | 7jvr.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/jv/7jvr ftp://data.pdbj.org/pub/pdb/validation_reports/jv/7jvr | 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 (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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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.) Homo sapiens (human) / Gene: GNAI1 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P63096 |
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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.) Homo sapiens (human) / Gene: GNB1 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P62873 |
#4: Protein | Mass: 7861.143 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: GNG2 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P59768 |
-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.) Escherichia coli (E. coli), (gene. exp.) Homo sapiens (human) Gene: cybC, DRD2 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P0ABE7, UniProt: P14416 |
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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: Escherichia coli (E. coli) |
#6: Chemical | ChemComp-08Y / |
-Details
Has ligand of interest | Y |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-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: Homo sapiens (human) |
Source (recombinant) | Organism: Spodoptera frugiperda (fall armyworm) |
Buffer solution | pH: 7.2 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
-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: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELDBright-field microscopy |
Image recording | Electron dose: 64 e/Å2 / Film or detector model: GATAN K2 BASE (4k x 4k) |
-Processing
Software | Name: PHENIX / Version: 1.13_2998: / Classification: refinement |
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CTF correction | Type: NONE |
3D reconstruction | Resolution: 2.8 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 632558 / Symmetry type: POINT |