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Yorodumi- EMDB-21243: Structure of a D2 dopamine receptor-G-protein complex in a lipid ... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-21243 | |||||||||
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Title | Structure of a D2 dopamine receptor-G-protein complex in a lipid membrane | |||||||||
Map data | Catecholamine receptor structure | |||||||||
Sample |
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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 / auditory behavior / nervous system process involved in regulation of systemic arterial blood pressure / 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 / auditory behavior / nervous system process involved in regulation of systemic arterial blood pressure / 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 / Extra-nuclear estrogen signaling / Dopamine receptors / Adenylate cyclase inhibitory pathway / 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 / non-motile cilium / response to morphine / G protein-coupled receptor internalization / Adrenaline,noradrenaline inhibits insulin secretion / ADP signalling through P2Y purinoceptor 12 / G alpha (i) signalling events / adult walking behavior / negative regulation of synaptic transmission / response to iron ion / GTPase activating protein binding / dopamine uptake involved in synaptic transmission / pigmentation / ciliary membrane / temperature homeostasis / regulation of synaptic transmission, GABAergic / arachidonic acid secretion / positive regulation of neuroblast proliferation / dopamine metabolic process / 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 / 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 / long-term memory / regulation of cAMP-mediated signaling / 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 sodium ion transport / regulation of mitotic spindle organization / cellular response to forskolin / release of sequestered calcium ion into cytosol / viral release from host cell by cytolysis / synapse assembly / response to amphetamine / ionotropic glutamate receptor binding / excitatory postsynaptic potential Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) / Rattus norvegicus (Norway rat) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.8 Å | |||||||||
Authors | Yin J / Chen KM / Clark MJ / Hijazi M / Kumari P / Bai X / Sunahara RK / Barth P / Rosenbaum DM | |||||||||
Funding support | United States, 1 items
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Citation | Journal: Nature / Year: 2020 Title: Structure of a D2 dopamine receptor-G-protein complex in a lipid membrane. Authors: Jie Yin / Kuang-Yui M Chen / Mary J Clark / Mahdi Hijazi / Punita Kumari / Xiao-Chen Bai / Roger K Sunahara / Patrick Barth / Daniel M Rosenbaum / Abstract: The D2 dopamine receptor (DRD2) is a therapeutic target for Parkinson's disease and antipsychotic drugs. DRD2 is activated by the endogenous neurotransmitter dopamine and synthetic agonist drugs such ...The D2 dopamine receptor (DRD2) is a therapeutic target for Parkinson's disease and antipsychotic drugs. DRD2 is activated by the endogenous neurotransmitter dopamine and synthetic agonist drugs such as bromocriptine, leading to stimulation of G and inhibition of adenylyl cyclase. Here we used cryo-electron microscopy to elucidate the structure of an agonist-bound activated DRD2-G complex reconstituted into a phospholipid membrane. The extracellular ligand-binding site of DRD2 is remodelled in response to agonist binding, with conformational changes in extracellular loop 2, transmembrane domain 5 (TM5), TM6 and TM7, propagating to opening of the intracellular G-binding site. The DRD2-G structure represents, to our knowledge, the first experimental model of a G-protein-coupled receptor-G-protein complex embedded in a phospholipid bilayer, which serves as a benchmark to validate the interactions seen in previous detergent-bound structures. The structure also reveals interactions that are unique to the membrane-embedded complex, including helix 8 burial in the inner leaflet, ordered lysine and arginine side chains in the membrane interfacial regions, and lipid anchoring of the G protein in the membrane. Our model of the activated DRD2 will help to inform the design of subtype-selective DRD2 ligands for multiple human central nervous system disorders. | |||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_21243.map.gz | 78.3 MB | EMDB map data format | |
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Header (meta data) | emd-21243-v30.xml emd-21243.xml | 16.9 KB 16.9 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_21243_fsc.xml | 10.1 KB | Display | FSC data file |
Images | emd_21243.png | 18.8 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-21243 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-21243 | HTTPS FTP |
-Related structure data
Related structure data | 6vmsMC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_21243.map.gz / Format: CCP4 / Size: 83.7 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | Catecholamine receptor structure | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 0.83 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Sample components
-Entire : D2 dopamine receptor-G protein complex
Entire | Name: D2 dopamine receptor-G protein complex |
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Components |
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-Supramolecule #1: D2 dopamine receptor-G protein complex
Supramolecule | Name: D2 dopamine receptor-G protein complex / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#5 |
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Source (natural) | Organism: Homo sapiens (human) |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
-Macromolecule #1: 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: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Rattus norvegicus (Norway rat) |
Molecular weight | Theoretical: 40.382047 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
Sequence | String: MGCTLSAEDK AAVERSKMID RNLREDGEKA AREVKLLLLG AGESGKNTIV KQMKIIHEAG YSEEECKQYK AVVYSNTIQS IIAIIRAMG RLKIDFGDAA RADDARQLFV LAGAAEEGFM TAELAGVIKR LWKDSGVQAC FNRSREYQLN DSAAYYLNDL D RIAQPNYI ...String: MGCTLSAEDK AAVERSKMID RNLREDGEKA AREVKLLLLG AGESGKNTIV KQMKIIHEAG YSEEECKQYK AVVYSNTIQS IIAIIRAMG RLKIDFGDAA 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 THFTCA TDTKNVQFVF DAVTDVIIKN NLKDCGLF |
-Macromolecule #2: 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: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 37.41693 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
Sequence | String: MSELDQLRQE AEQLKNQIRD ARKACADATL SQITNNIDPV GRIQMRTRRT LRGHLAKIYA MHWGTDSRLL VSASQDGKLI IWDSYTTNK VHAIPLRSSW VMTCAYAPSG NYVACGGLDN ICSIYNLKTR EGNVRVSREL AGHTGYLSCC RFLDDNQIVT S SGDTTCAL ...String: MSELDQLRQE AEQLKNQIRD ARKACADATL SQITNNIDPV GRIQMRTRRT LRGHLAKIYA MHWGTDSRLL VSASQDGKLI IWDSYTTNK VHAIPLRSSW VMTCAYAPSG NYVACGGLDN ICSIYNLKTR EGNVRVSREL AGHTGYLSCC RFLDDNQIVT S SGDTTCAL WDIETGQQTT TFTGHTGDVM SLSLAPDTRL FVSGACDASA KLWDVREGMC RQTFTGHESD INAICFFPNG NA FATGSDD ATCRLFDLRA DQELMTYSHD NIICGITSVS FSKSGRLLLA GYDDFNCNVW DALKADRAGV LAGHDNRVSC LGV TDDGMA VATGSWDSFL KIWN |
-Macromolecule #3: 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: 3 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 9.137474 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
Sequence | String: MGHHHHHHHH GGASNNTASI AQARKLVEQL KMEANIDRIK VSKAAADLMA YCEAHAKEDP LLTPVPASEN PFREKKFFCA IL |
-Macromolecule #4: scFv16
Macromolecule | Name: scFv16 / type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 27.784896 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
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 KAAAHHHHHH HH |
-Macromolecule #5: Endolysin,D(2) dopamine receptor,D(2) dopamine receptor
Macromolecule | Name: Endolysin,D(2) dopamine receptor,D(2) dopamine receptor type: protein_or_peptide / ID: 5 / Number of copies: 1 / Enantiomer: LEVO / EC number: lysozyme |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 51.384059 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
Sequence | String: DYKDDDDANI FEMLRIDEGL RLKIYKNTEG YYTIGIGHLL TKSPSLNAAK SELDKAIGRN TNGVITKDEA EKLFNQDVDA AVRGILRNA KLKPVYDSLD AVRRAALINM VFQMGETGVA GFTNSLRMLQ QKRWDEAAVN LAKSRWYNQT PNRAKRVITT F RTGTWDAY ...String: DYKDDDDANI FEMLRIDEGL RLKIYKNTEG YYTIGIGHLL TKSPSLNAAK SELDKAIGRN TNGVITKDEA EKLFNQDVDA AVRGILRNA KLKPVYDSLD AVRRAALINM VFQMGETGVA GFTNSLRMLQ QKRWDEAAVN LAKSRWYNQT PNRAKRVITT F RTGTWDAY AADRPHYNYY ATLLTLLIAV IVFGNVLVCM AVSREKALQT TTNYLIVSLA VADLLVATLV MPWVVYLEVV GE WKFSRIH CDIFVTLDVM MCTASILNLC AISIDRYTAV AMPMLYNTRY SSKRRVTVMI SIVWVLSFTI SCPLLFGLNN ADQ NECIIA NPAFVVYSSI VSFYVPFIVI LLVYIKIYIV LRRRRKLVNT NRKLSQQKEK KATQLLAIYL GLFIICWLPF FITH ILNIH CDCNIPPVLY SAFTWLGYVN SAINPIIYTT FNIEFRKAFL KILHC |
-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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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.4 |
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Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy |
Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 64.0 e/Å2 |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |