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Open data
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Basic information
Entry | Database: PDB / ID: 7cmu | ||||||
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Title | Dopamine Receptor D3R-Gi-Pramipexole complex | ||||||
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![]() | MEMBRANE PROTEIN / G protein-coupled receptor / Dopamine receptor | ||||||
Function / homology | ![]() musculoskeletal movement, spinal reflex action / acid secretion / dopamine neurotransmitter receptor activity, coupled via Gi/Go / response to histamine / regulation of potassium ion transport / Dopamine receptors / adenylate cyclase-inhibiting dopamine receptor signaling pathway / regulation of dopamine uptake involved in synaptic transmission / positive regulation of dopamine receptor signaling pathway / phospholipase C-activating dopamine receptor signaling pathway ...musculoskeletal movement, spinal reflex action / acid secretion / dopamine neurotransmitter receptor activity, coupled via Gi/Go / response to histamine / regulation of potassium ion transport / Dopamine receptors / adenylate cyclase-inhibiting dopamine receptor signaling pathway / regulation of dopamine uptake involved in synaptic transmission / positive regulation of dopamine receptor signaling pathway / phospholipase C-activating dopamine receptor signaling pathway / negative regulation of oligodendrocyte differentiation / negative regulation of synaptic transmission, glutamatergic / G protein-coupled receptor internalization / response to morphine / arachidonic acid secretion / dopamine metabolic process / negative regulation of cytosolic calcium ion concentration / regulation of dopamine secretion / positive regulation of cytokinesis / social behavior / behavioral response to cocaine / negative regulation of protein secretion / Adenylate cyclase inhibitory pathway / positive regulation of protein localization to cell cortex / negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / regulation of cAMP-mediated signaling / D2 dopamine receptor binding / prepulse inhibition / G protein-coupled serotonin receptor binding / adenylate cyclase-activating adrenergic receptor signaling pathway / regulation of mitotic spindle organization / cellular response to forskolin / negative regulation of blood pressure / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / positive regulation of mitotic nuclear division / response to cocaine / learning / locomotory behavior / Regulation of insulin secretion / G protein-coupled receptor binding / G protein-coupled receptor activity / electron transport chain / circadian regulation of gene expression / G-protein beta/gamma-subunit complex binding / visual learning / Olfactory Signaling Pathway / Activation of the phototransduction cascade / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / 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 / 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 / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / Sensory perception of sweet, bitter, and umami (glutamate) taste / response to peptide hormone / photoreceptor disc membrane / Adrenaline,noradrenaline inhibits insulin secretion / Glucagon-type ligand receptors / Vasopressin regulates renal water homeostasis via Aquaporins / intracellular calcium ion homeostasis / 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 / adenylate cyclase-activating dopamine receptor signaling pathway / G beta:gamma signalling through PI3Kgamma / cellular response to prostaglandin E stimulus / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / GPER1 signaling / GDP binding / G-protein beta-subunit binding / Inactivation, recovery and regulation of the phototransduction cascade / heterotrimeric G-protein complex / G alpha (12/13) signalling events / extracellular vesicle / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / GTPase binding / retina development in camera-type eye / phospholipase C-activating G protein-coupled receptor signaling pathway / Ca2+ pathway / cell cortex / midbody / G alpha (i) signalling events / fibroblast proliferation / G alpha (s) signalling events / G alpha (q) signalling events / cell population proliferation / Ras protein signal transduction / Extra-nuclear estrogen signaling Similarity search - Function | ||||||
Biological species | ![]() ![]() ![]() ![]() ![]() | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3 Å | ||||||
![]() | Xu, P. / Huang, S. / Mao, C. / Krumm, B. / Zhou, X. / Tan, Y. / Huang, X.-P. / Liu, Y. / Shen, D.-D. / Jiang, Y. ...Xu, P. / Huang, S. / Mao, C. / Krumm, B. / Zhou, X. / Tan, Y. / Huang, X.-P. / Liu, Y. / Shen, D.-D. / Jiang, Y. / Yu, X. / Jiang, H. / Melcher, K. / Roth, B. / Cheng, X. / Zhang, Y. / Xu, H. | ||||||
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![]() | ![]() Title: Structures of the human dopamine D3 receptor-G complexes. Authors: Peiyu Xu / Sijie Huang / Chunyou Mao / Brian E Krumm / X Edward Zhou / Yangxia Tan / Xi-Ping Huang / Yongfeng Liu / Dan-Dan Shen / Yi Jiang / Xuekui Yu / Hualiang Jiang / Karsten Melcher / ...Authors: Peiyu Xu / Sijie Huang / Chunyou Mao / Brian E Krumm / X Edward Zhou / Yangxia Tan / Xi-Ping Huang / Yongfeng Liu / Dan-Dan Shen / Yi Jiang / Xuekui Yu / Hualiang Jiang / Karsten Melcher / Bryan L Roth / Xi Cheng / Yan Zhang / H Eric Xu / ![]() ![]() Abstract: The dopamine system, including five dopamine receptors (D1R-D5R), plays essential roles in the central nervous system (CNS), and ligands that activate dopamine receptors have been used to treat many ...The dopamine system, including five dopamine receptors (D1R-D5R), plays essential roles in the central nervous system (CNS), and ligands that activate dopamine receptors have been used to treat many neuropsychiatric disorders. Here, we report two cryo-EM structures of human D3R in complex with an inhibitory G protein and bound to the D3R-selective agonists PD128907 and pramipexole, the latter of which is used to treat patients with Parkinson's disease. The structures reveal agonist binding modes distinct from the antagonist-bound D3R structure and conformational signatures for ligand-induced receptor activation. Mutagenesis and homology modeling illuminate determinants of ligand specificity across dopamine receptors and the mechanisms for G protein coupling. Collectively our work reveals the basis of agonist binding and ligand-induced receptor activation and provides structural templates for designing specific ligands to treat CNS diseases targeting the dopaminergic system. | ||||||
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Structure visualization
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Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 212 KB | Display | ![]() |
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PDB format | ![]() | 168 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 794.9 KB | Display | ![]() |
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Full document | ![]() | 799.8 KB | Display | |
Data in XML | ![]() | 33.2 KB | Display | |
Data in CIF | ![]() | 51.2 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 30410MC ![]() 7cmvC 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
#1: Protein | Mass: 40414.047 Da / Num. of mol.: 1 / Mutation: S47N, G203A, E245A, A326S Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
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#2: Protein | Mass: 37915.496 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
#3: Protein | Mass: 7861.143 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
-Antibody / Protein / Non-polymers , 3 types, 3 molecules ER![](data/chem/img/G6L.gif)
![](data/chem/img/G6L.gif)
#4: Antibody | Mass: 26466.486 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() |
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#5: Protein | Mass: 60816.801 Da / Num. of mol.: 1 / Mutation: M35W,H130I,R134L Source method: isolated from a genetically manipulated source Details: chimera protein of Soluble cytochrome b562 and D(3) dopamine receptor Source: (gene. exp.) ![]() ![]() ![]() Gene: cybC, DRD3 / Production host: ![]() ![]() |
#6: Chemical | ChemComp-G6L / ( |
-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 |
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Sample preparation
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Buffer solution | pH: 7.4 | ||||||||||||||||||||||||||||||
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||||||||||||||||
Specimen support | Grid material: GOLD / Grid type: UltrAuFoil R1.2/1.3 | ||||||||||||||||||||||||||||||
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 SUMMIT (4k x 4k) |
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Processing
CTF correction | Type: NONE |
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3D reconstruction | Resolution: 3 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 135278 / Symmetry type: POINT |