[English] 日本語
Yorodumi- PDB-7jvr: Cryo-EM structure of Bromocriptine-bound dopamine receptor 2 in c... -
+Open data
-Basic information
Entry | Database: PDB / ID: 7jvr | |||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Title | Cryo-EM structure of Bromocriptine-bound dopamine receptor 2 in complex with Gi protein | |||||||||||||||
Components |
| |||||||||||||||
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 / positive regulation of glial cell-derived neurotrophic factor production / acid secretion / regulation of synapse structural plasticity / auditory behavior / nervous system process involved in regulation of systemic arterial blood pressure / dopamine neurotransmitter receptor activity, coupled via Gi/Go ...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 / positive regulation of glial cell-derived neurotrophic factor production / acid secretion / regulation of synapse structural plasticity / auditory behavior / nervous system process involved in regulation of systemic arterial blood pressure / dopamine neurotransmitter receptor activity, coupled via Gi/Go / response to histamine / neuron-neuron synaptic transmission / adenohypophysis development / positive regulation of renal sodium excretion / cerebral cortex GABAergic interneuron migration / hyaloid vascular plexus regression / negative regulation of neuron migration / regulation of potassium ion transport / negative regulation of cellular response to hypoxia / adenylate cyclase-inhibiting dopamine receptor signaling pathway / orbitofrontal cortex development / response to inactivity / Dopamine receptors / branching morphogenesis of a nerve / negative regulation of voltage-gated calcium channel activity / regulation of dopamine uptake involved in synaptic transmission / dopamine binding / negative regulation of dopamine secretion / positive regulation of growth hormone secretion / heterotrimeric G-protein binding / behavioral response to ethanol / drinking behavior / G protein-coupled receptor complex / peristalsis / phospholipase C-activating dopamine receptor signaling pathway / grooming behavior / dopaminergic synapse / 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 / G protein-coupled receptor internalization / positive regulation of multicellular organism growth / non-motile cilium / adult walking behavior / response to iron ion / response to morphine / ciliary membrane / pigmentation / regulation of synaptic transmission, GABAergic / arachidonate secretion / temperature homeostasis / postsynaptic modulation of chemical synaptic transmission / positive regulation of neuroblast proliferation / heterocyclic compound binding / dopamine uptake involved in synaptic transmission / regulation of dopamine secretion / negative regulation of cytosolic calcium ion concentration / dopamine metabolic process / adenylate cyclase-activating adrenergic receptor signaling pathway / positive regulation of cytokinesis / positive regulation of receptor internalization / associative learning / behavioral response to cocaine / endocytic vesicle / negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / response to light stimulus / lateral plasma membrane / neuroblast proliferation / G-protein alpha-subunit binding / sperm flagellum / response to axon injury / potassium channel regulator activity / T cell migration / negative regulation of protein secretion / Adenylate cyclase inhibitory pathway / positive regulation of protein localization to cell cortex / negative regulation of insulin secretion / regulation of cAMP-mediated signaling / long-term memory / prepulse inhibition / D2 dopamine receptor binding / G protein-coupled serotonin receptor binding / GABA-ergic synapse / regulation of sodium ion transport / release of sequestered calcium ion into cytosol / axon terminus / regulation of mitotic spindle organization / cellular response to forskolin / synapse assembly / presynaptic modulation of chemical synaptic transmission / negative regulation of blood pressure / negative regulation of innate immune response / ionotropic glutamate receptor binding / response to amphetamine / phosphatidylinositol 3-kinase/protein kinase B signal transduction / regulation of heart rate / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / acrosomal vesicle 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
| |||||||||||||||
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 |
|
-Structure visualization
Movie |
Movie viewer |
---|---|
Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 7jvr.cif.gz | 238.9 KB | Display | PDBx/mmCIF format |
---|---|---|---|---|
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
Summary document | 7jvr_validation.pdf.gz | 812.8 KB | Display | wwPDB validaton report |
---|---|---|---|---|
Full document | 7jvr_full_validation.pdf.gz | 820 KB | Display | |
Data in XML | 7jvr_validation.xml.gz | 34 KB | Display | |
Data in CIF | 7jvr_validation.cif.gz | 52.6 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/jv/7jvr ftp://data.pdbj.org/pub/pdb/validation_reports/jv/7jvr | HTTPS FTP |
-Related structure data
Related structure data | 22511MC 7jv5C 7jvpC 7jvqC M: map data used to model this data C: citing same article (ref.) |
---|---|
Similar structure data |
-Links
-Assembly
Deposited unit |
|
---|---|
1 |
|
-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 |
---|---|
#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 |
---|---|
#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 |
---|
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
---|---|
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 |
---|---|
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 |
---|---|
Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD |
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 |
---|---|
CTF correction | Type: NONE |
3D reconstruction | Resolution: 2.8 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 632558 / Symmetry type: POINT |