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Yorodumi- EMDB-31404: Cryo-EM structure of dopamine receptor 1 and mini-Gs complex with... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-31404 | |||||||||
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Title | Cryo-EM structure of dopamine receptor 1 and mini-Gs complex with dopamine bound | |||||||||
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Sample |
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Function / homology | Function and homology information dopamine neurotransmitter receptor activity / cerebral cortex GABAergic interneuron migration / Dopamine receptors / operant conditioning / dopamine neurotransmitter receptor activity, coupled via Gs / dopamine binding / regulation of dopamine uptake involved in synaptic transmission / modification of postsynaptic structure / heterotrimeric G-protein binding / regulation of dopamine metabolic process ...dopamine neurotransmitter receptor activity / cerebral cortex GABAergic interneuron migration / Dopamine receptors / operant conditioning / dopamine neurotransmitter receptor activity, coupled via Gs / dopamine binding / regulation of dopamine uptake involved in synaptic transmission / modification of postsynaptic structure / heterotrimeric G-protein binding / regulation of dopamine metabolic process / sensitization / peristalsis / G protein-coupled receptor complex / phospholipase C-activating dopamine receptor signaling pathway / dopamine transport / grooming behavior / positive regulation of neuron migration / habituation / astrocyte development / conditioned taste aversion / positive regulation of potassium ion transport / striatum development / dentate gyrus development / maternal behavior / arrestin family protein binding / non-motile cilium / adult walking behavior / mating behavior / long-term synaptic depression / ciliary membrane / G protein-coupled dopamine receptor signaling pathway / temperature homeostasis / dopamine metabolic process / transmission of nerve impulse / glucose import / PKA activation in glucagon signalling / behavioral response to cocaine / G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / hair follicle placode formation / mu-type opioid receptor binding / developmental growth / corticotropin-releasing hormone receptor 1 binding / G-protein alpha-subunit binding / intracellular transport / D1 dopamine receptor binding / GABA-ergic synapse / neuronal action potential / behavioral fear response / Hedgehog 'off' state / prepulse inhibition / beta-2 adrenergic receptor binding / adenylate cyclase-activating adrenergic receptor signaling pathway / synapse assembly / response to amphetamine / activation of adenylate cyclase activity / adenylate cyclase activator activity / presynaptic modulation of chemical synaptic transmission / positive regulation of synaptic transmission, glutamatergic / positive regulation of release of sequestered calcium ion into cytosol / trans-Golgi network membrane / synaptic transmission, glutamatergic / G protein-coupled receptor activity / long-term synaptic potentiation / regulation of protein phosphorylation / insulin-like growth factor receptor binding / ionotropic glutamate receptor binding / G-protein beta/gamma-subunit complex binding / visual learning / bone development / Olfactory Signaling Pathway / Activation of the phototransduction cascade / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / adenylate cyclase-activating G protein-coupled receptor signaling pathway / 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 / memory / cognition / 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 / cilium / photoreceptor disc membrane / platelet aggregation / Adrenaline,noradrenaline inhibits insulin secretion / Glucagon-type ligand receptors / Vasopressin regulates renal water homeostasis via Aquaporins / 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 Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) / synthetic construct (others) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.1 Å | |||||||||
Authors | Xiao T / Zheng S | |||||||||
Funding support | China, 1 items
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Citation | Journal: Sci Adv / Year: 2022 Title: Structural insights into G protein activation by D1 dopamine receptor. Authors: Xiao Teng / Sijia Chen / Qing Wang / Zhao Chen / Xiaoying Wang / Niu Huang / Sanduo Zheng / Abstract: G protein-coupled receptors (GPCRs) comprise the largest family of membrane receptors and are the most important drug targets. An agonist-bound GPCR engages heterotrimeric G proteins and triggers the ...G protein-coupled receptors (GPCRs) comprise the largest family of membrane receptors and are the most important drug targets. An agonist-bound GPCR engages heterotrimeric G proteins and triggers the exchange of guanosine diphosphate (GDP) with guanosine triphosphate (GTP) to promote G protein activation. A complete understanding of molecular mechanisms of G protein activation has been hindered by a lack of structural information of GPCR-G protein complex in nucleotide-bound states. Here, we report the cryo-EM structures of the D1 dopamine receptor and mini-G complex in the nucleotide-free and nucleotide-bound states. These structures reveal major conformational changes in Gα such as structural rearrangements of the carboxyl- and amino-terminal α helices that account for the release of GDP and the GTP-dependent dissociation of Gα from Gβγ subunits. As validated by biochemical and cellular signaling studies, our structures shed light into the molecular basis of the entire signaling events of GPCR-mediated G protein activation. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_31404.map.gz | 20.9 MB | EMDB map data format | |
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Header (meta data) | emd-31404-v30.xml emd-31404.xml | 14.5 KB 14.5 KB | Display Display | EMDB header |
Images | emd_31404.png | 38.5 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-31404 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-31404 | HTTPS FTP |
-Validation report
Summary document | emd_31404_validation.pdf.gz | 410.3 KB | Display | EMDB validaton report |
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Full document | emd_31404_full_validation.pdf.gz | 409.8 KB | Display | |
Data in XML | emd_31404_validation.xml.gz | 5.8 KB | Display | |
Data in CIF | emd_31404_validation.cif.gz | 6.5 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-31404 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-31404 | HTTPS FTP |
-Related structure data
Related structure data | 7f0tMC 7f1oC 7f1zC 7f23C 7f24C M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_31404.map.gz / Format: CCP4 / Size: 22.2 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Voxel size | X=Y=Z: 1.087 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Sample components
-Entire : Cryo-EM structure of dopamine receptor 1 and mini-Gs complex with...
Entire | Name: Cryo-EM structure of dopamine receptor 1 and mini-Gs complex with dopamine bound |
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Components |
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-Supramolecule #1: Cryo-EM structure of dopamine receptor 1 and mini-Gs complex with...
Supramolecule | Name: Cryo-EM structure of dopamine receptor 1 and mini-Gs complex with dopamine bound type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#5 |
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Source (natural) | Organism: Homo sapiens (human) |
-Macromolecule #1: D(1A) dopamine receptor
Macromolecule | Name: D(1A) dopamine receptor / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 52.409656 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MKTIIALSYI FCLVFADYKD DDDASIDMRT LNTSAMDGTG LVVERDFSVR ILTACFLSLL ILSTLLGNTL VCAAVIRFRH LRSKVTNFF VISLAVSDLL VAVLVMPWKA VAEIAGFWPF GSFCNIWVAF DIMCSTASIL NLCVISVDRY WAISSPFRYE R KMTPKAAF ...String: MKTIIALSYI FCLVFADYKD DDDASIDMRT LNTSAMDGTG LVVERDFSVR ILTACFLSLL ILSTLLGNTL VCAAVIRFRH LRSKVTNFF VISLAVSDLL VAVLVMPWKA VAEIAGFWPF GSFCNIWVAF DIMCSTASIL NLCVISVDRY WAISSPFRYE R KMTPKAAF ILISVAWTLS VLISFIPVQL SWHKAKPTSP SDGNATSLAE TIDNCDSSLS RTYAISSSVI SFYIPVAIMI VT YTRIYRI AQKQIRRIAA LERAAVHAKN CQTTTGNGKP VECSQPESSF KMSFKRETKV LKTLSVIMGV FVCCWLPFFI LNC ILPFCG SGETQPFCID SNTFDVFVWF GWANSSLNPI IYAFNADFRK AFSTLLGCYR LCPATNNAIE TVSINNNGAA MFSS HHEPR GSISKECNLV YLIPHAVGSS EDLKKEEAAG IARPLEKLSP ALSVILDYDT DVSLEKIQPI TQNGQHPT |
-Macromolecule #2: Guanine nucleotide-binding protein G(s) subunit alpha isoforms sh...
Macromolecule | Name: Guanine nucleotide-binding protein G(s) subunit alpha isoforms short,Isoform Gnas-2 of Guanine nucleotide-binding protein G(s) subunit alpha isoforms short 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: 28.907684 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: NSKTEDQRNE EKAQREANKK IEKQLQKDKQ VYRATHRLLL LGADNSGKST IVKQMRILHG GSGGSGGTSG IFETKFQVDK VNFHMFDVG GQRDERRKWI QCFNDVTAII FVVDSSDYNR LQEALNLFKS IWNNRWLRTI SVILFLNKQD LLAEKVLAGK S KIEDYFPE ...String: NSKTEDQRNE EKAQREANKK IEKQLQKDKQ VYRATHRLLL LGADNSGKST IVKQMRILHG GSGGSGGTSG IFETKFQVDK VNFHMFDVG GQRDERRKWI QCFNDVTAII FVVDSSDYNR LQEALNLFKS IWNNRWLRTI SVILFLNKQD LLAEKVLAGK S KIEDYFPE FARYTTPEDA TPEPGEDPRV TRAKYFIRDE FLRISTASGD GRHYCYPHFT CAVDTENARR IFNDCRDIIQ RM HLRQYEL L |
-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: Homo sapiens (human) |
Molecular weight | Theoretical: 39.418086 KDa |
Recombinant expression | Organism: Trichoplusia ni (cabbage looper) |
Sequence | String: MHHHHHHLEV LFQGPGSSGS ELDQLRQEAE QLKNQIRDAR KACADATLSQ ITNNIDPVGR IQMRTRRTLR GHLAKIYAMH WGTDSRLLV SASQDGKLII WDSYTTNKVH AIPLRSSWVM TCAYAPSGNY VACGGLDNIC SIYNLKTREG NVRVSRELAG H TGYLSCCR ...String: MHHHHHHLEV LFQGPGSSGS ELDQLRQEAE QLKNQIRDAR KACADATLSQ ITNNIDPVGR IQMRTRRTLR GHLAKIYAMH WGTDSRLLV SASQDGKLII WDSYTTNKVH AIPLRSSWVM TCAYAPSGNY VACGGLDNIC SIYNLKTREG NVRVSRELAG H TGYLSCCR FLDDNQIVTS SGDTTCALWD IETGQQTTTF TGHTGDVMSL SLAPDTRLFV SGACDASAKL WDVREGMCRQ TF TGHESDI NAICFFPNGN AFATGSDDAT CRLFDLRADQ ELMTYSHDNI ICGITSVSFS KSGRLLLAGY DDFNCNVWDA LKA DRAGVL AGHDNRVSCL GVTDDGMAVA TGSWDSFLKI WN |
-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: Homo sapiens (human) |
Molecular weight | Theoretical: 7.845078 KDa |
Recombinant expression | Organism: Trichoplusia ni (cabbage looper) |
Sequence | String: MASNNTASIA QARKLVEQLK MEANIDRIKV SKAAADLMAY CEAHAKEDPL LTPVPASENP FREKKFFSAI L |
-Macromolecule #5: Nanobody35
Macromolecule | Name: Nanobody35 / 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: 17.352498 KDa |
Recombinant expression | Organism: Escherichia coli (E. coli) |
Sequence | String: MKYLLPTAAA GLLLLAAQPA MAQVQLQESG GGLVQPGGSL RLSCAASGFT FSNYKMNWVR QAPGKGLEWV SDISQSGASI SYTGSVKGR FTISRDNAKN TLYLQMNSLK PEDTAVYYCA RCPAPFTRDC FDVTSTTYAY RGQGTQVTVS SHHHHHHEPE A |
-Macromolecule #6: L-DOPAMINE
Macromolecule | Name: L-DOPAMINE / type: ligand / ID: 6 / Number of copies: 1 / Formula: LDP |
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Molecular weight | Theoretical: 153.178 Da |
Chemical component information | ChemComp-LDP: |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 4.0 mg/mL |
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Buffer | pH: 7.5 |
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 281 K / Instrument: FEI VITROBOT MARK IV |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 50.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.1 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 1045088 |
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Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |