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- EMDB-22511: 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: EMDB / ID: EMD-22511 | |||||||||||||||
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Title | Cryo-EM structure of Bromocriptine-bound dopamine receptor 2 in complex with Gi protein | |||||||||||||||
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![]() | Dopamine receptor 2 / Gi protein / bromocriptine / SIGNALING PROTEIN | |||||||||||||||
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 / response to histamine / regulation of synapse structural plasticity ...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 / response to histamine / regulation of synapse structural plasticity / 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 / regulation of potassium ion transport / hyaloid vascular plexus regression / negative regulation of dopamine secretion / adenylate cyclase-inhibiting dopamine receptor signaling pathway / response to inactivity / orbitofrontal cortex development / cerebral cortex GABAergic interneuron migration / Dopamine receptors / positive regulation of growth hormone secretion / negative regulation of neuron migration / dopamine binding / branching morphogenesis of a nerve / regulation of dopamine uptake involved in synaptic transmission / phospholipase C-activating dopamine receptor signaling pathway / peristalsis / heterotrimeric G-protein binding / 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 / positive regulation of urine volume / positive regulation of multicellular organism growth / G protein-coupled receptor internalization / negative regulation of synaptic transmission, glutamatergic / non-motile cilium / heterocyclic compound binding / response to iron ion / adult walking behavior / arachidonate secretion / response to morphine / ciliary membrane / negative regulation of cytosolic calcium ion concentration / temperature homeostasis / pigmentation / positive regulation of neuroblast proliferation / positive regulation of cytokinesis / dopamine uptake involved in synaptic transmission / regulation of synaptic transmission, GABAergic / regulation of dopamine secretion / dopamine metabolic process / cellular response to ethanol / response to light stimulus / associative learning / positive regulation of receptor internalization / sperm flagellum / lateral plasma membrane / endocytic vesicle / G-protein alpha-subunit binding / neuroblast proliferation / negative regulation of protein secretion / long-term memory / potassium channel regulator activity / postsynaptic modulation of chemical synaptic transmission / prepulse inhibition / response to axon injury / adenylate cyclase inhibitor activity / behavioral response to cocaine / positive regulation of protein localization to cell cortex / regulation of sodium ion transport / T cell migration / Adenylate cyclase inhibitory pathway / synapse assembly / D2 dopamine receptor binding / response to prostaglandin E / negative regulation of blood pressure / G protein-coupled serotonin receptor binding / adenylate cyclase regulator activity / cellular response to retinoic acid / adenylate cyclase-inhibiting serotonin receptor signaling pathway / axon terminus / release of sequestered calcium ion into cytosol / presynaptic modulation of chemical synaptic transmission / ionotropic glutamate receptor binding / response to amphetamine / cellular response to forskolin / negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / axonogenesis / regulation of heart rate / regulation of mitotic spindle organization / negative regulation of innate immune response / negative regulation of cell migration Similarity search - Function | |||||||||||||||
Biological species | ![]() | |||||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.8 Å | |||||||||||||||
![]() | Zhuang Y / Xu P | |||||||||||||||
Funding support | ![]() ![]()
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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
Movie |
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Structure viewer | EM map: ![]() ![]() ![]() |
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 26.4 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 20.8 KB 20.8 KB | Display Display | ![]() |
Images | ![]() | 63.8 KB | ||
Filedesc metadata | ![]() | 7.3 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 394.2 KB | Display | ![]() |
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Full document | ![]() | 393.8 KB | Display | |
Data in XML | ![]() | 5.6 KB | Display | |
Data in CIF | ![]() | 6.4 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7jvrMC ![]() 7jv5C ![]() 7jvpC ![]() 7jvqC 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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Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.045 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 : Bromocriptin-bound dopamine receptor 2 in complex with Gi protein
Entire | Name: Bromocriptin-bound dopamine receptor 2 in complex with Gi protein |
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Components |
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-Supramolecule #1: Bromocriptin-bound dopamine receptor 2 in complex with Gi protein
Supramolecule | Name: Bromocriptin-bound dopamine receptor 2 in complex with Gi protein type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#5 |
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Source (natural) | Organism: ![]() |
-Macromolecule #1: Soluble cytochrome b562,D(2) dopamine receptor
Macromolecule | Name: Soluble cytochrome b562,D(2) dopamine receptor / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 67.234578 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: DYKDDDDAKL QTMHHHHHHH HHHHHHHHAD LEDNWETLND NLKVIEKADN AAQVKDALTK MRAAALDAQK ATPPKLEDKS PDSPEMKDF RHGFDILVGQ IDDALKLANE GKVKEAQAAA EQLKTTRNAY IQKYLASENL YFQGGTMDPL NLSWYDDDLE R QNWSRPFN ...String: DYKDDDDAKL QTMHHHHHHH HHHHHHHHAD LEDNWETLND NLKVIEKADN AAQVKDALTK MRAAALDAQK ATPPKLEDKS PDSPEMKDF RHGFDILVGQ IDDALKLANE GKVKEAQAAA EQLKTTRNAY IQKYLASENL YFQGGTMDPL NLSWYDDDLE R QNWSRPFN GSDGKADRPH YNYYATLLTL LIAVIVFGNV LVCMAVSREK ALQTTTNYLI VSLAVADLLV ATLVMPWVVY LE VVGEWKF SRIHCDIFVT LDVMMCTASI LNLCAISIDR YTAVAMPMLY NTRYSSKRRV TVMISIVWVL SFTISCPLLF GLN NADQNE CIIANPAFVV YSSIVSFYVP FIVTLLVYIK IYIVLRRRRK RVNTKRSSRA FRAHLRAPLK GNCTHPEDMK LCTV IMKSN GSFPVNRRRV EAARRAQELE MEMLSSTSPP ERTRYSPIPP SHHQLTLPDP SHHGLHSTPD SPAKPEKNGH AKDHP KIAK IFEIQTMPNG KTRTSLKTMS RRKLSQQKEK KATQMLAIVL GVFIICWLPF FITHILNIHC DCNIPPVLYS AFTWLG YVN SAVNPIIYTT FNIEFRKAFL KILHC UniProtKB: Soluble cytochrome b562, D(2) dopamine receptor |
-Macromolecule #2: Guanine nucleotide-binding protein G(i) subunit alpha-1
Macromolecule | Name: Guanine nucleotide-binding protein G(i) subunit alpha-1 type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 40.414047 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: MGCTLSAEDK AAVERSKMID RNLREDGEKA AREVKLLLLG AGESGKNTIV KQMKIIHEAG YSEEECKQYK AVVYSNTIQS IIAIIRAMG RLKIDFGDSA RADDARQLFV LAGAAEEGFM TAELAGVIKR LWKDSGVQAC FNRSREYQLN DSAAYYLNDL D RIAQPNYI ...String: MGCTLSAEDK AAVERSKMID RNLREDGEKA AREVKLLLLG AGESGKNTIV KQMKIIHEAG YSEEECKQYK AVVYSNTIQS IIAIIRAMG RLKIDFGDSA RADDARQLFV LAGAAEEGFM TAELAGVIKR LWKDSGVQAC FNRSREYQLN DSAAYYLNDL D RIAQPNYI PTQQDVLRTR VKTTGIVETH FTFKDLHFKM FDVGAQRSER KKWIHCFEGV TAIIFCVALS DYDLVLAEDE EM NRMHASM KLFDSICNNK WFTDTSIILF LNKKDLFEEK IKKSPLTICY PEYAGSNTYE EAAAYIQCQF EDLNKRKDTK EIY THFTCS TDTKNVQFVF DAVTDVIIKN NLKDCGLF UniProtKB: Guanine nucleotide-binding protein G(i) subunit alpha-1 |
-Macromolecule #3: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
Macromolecule | Name: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 38.146707 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: MGSLLQSELD QLRQEAEQLK NQIRDARKAC ADATLSQITN NIDPVGRIQM RTRRTLRGHL AKIYAMHWGT DSRLLVSASQ DGKLIIWDS YTTNKVHAIP LRSSWVMTCA YAPSGNYVAC GGLDNICSIY NLKTREGNVR VSRELAGHTG YLSCCRFLDD N QIVTSSGD ...String: MGSLLQSELD QLRQEAEQLK NQIRDARKAC ADATLSQITN NIDPVGRIQM RTRRTLRGHL AKIYAMHWGT DSRLLVSASQ DGKLIIWDS YTTNKVHAIP LRSSWVMTCA YAPSGNYVAC GGLDNICSIY NLKTREGNVR VSRELAGHTG YLSCCRFLDD N QIVTSSGD TTCALWDIET GQQTTTFTGH TGDVMSLSLA PDTRLFVSGA CDASAKLWDV REGMCRQTFT GHESDINAIC FF PNGNAFA TGSDDATCRL FDLRADQELM TYSHDNIICG ITSVSFSKSG RLLLAGYDDF NCNVWDALKA DRAGVLAGHD NRV SCLGVT DDGMAVATGS WDSFLKIWNG SS UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 |
-Macromolecule #4: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
Macromolecule | Name: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 7.861143 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: MASNNTASIA QARKLVEQLK MEANIDRIKV SKAAADLMAY CEAHAKEDPL LTPVPASENP FREKKFFCAI L UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 |
-Macromolecule #5: Antibody fragment ScFv16
Macromolecule | Name: Antibody fragment ScFv16 / type: protein_or_peptide / ID: 5 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: synthetic construct (others) |
Molecular weight | Theoretical: 28.813047 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: DVQLVESGGG LVQPGGSRKL SCSASGFAFS SFGMHWVRQA PEKGLEWVAY ISSGSGTIYY ADTVKGRFTI SRDDPKNTLF LQMTSLRSE DTAMYYCVRS IYYYGSSPFD FWGQGTTLTV SSGGGGSGGG GSGGGGSDIV MTQATSSVPV TPGESVSISC R SSKSLLHS ...String: DVQLVESGGG LVQPGGSRKL SCSASGFAFS SFGMHWVRQA PEKGLEWVAY ISSGSGTIYY ADTVKGRFTI SRDDPKNTLF LQMTSLRSE DTAMYYCVRS IYYYGSSPFD FWGQGTTLTV SSGGGGSGGG GSGGGGSDIV MTQATSSVPV TPGESVSISC R SSKSLLHS NGNTYLYWFL QRPGQSPQLL IYRMSNLASG VPDRFSGSGS GTAFTLTISR LEAEDVGVYY CMQHLEYPLT FG AGTKLEL KGSLEVLFQG PAAAHHHHHH HH |
-Macromolecule #6: bromoergocryptine
Macromolecule | Name: bromoergocryptine / type: ligand / ID: 6 / Number of copies: 1 / Formula: 08Y |
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Molecular weight | Theoretical: 654.594 Da |
Chemical component information | ![]() ChemComp-08Y: |
-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: 7.2 |
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Vitrification | Cryogen name: ETHANE |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K2 BASE (4k x 4k) / Average electron dose: 64.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |