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- EMDB-31427: Cryo-EM structure of the GTP-bound dopamine receptor 1 and mini-G... -
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Basic information
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Title | Cryo-EM structure of the GTP-bound dopamine receptor 1 and mini-Gs complex without Nb35 | |||||||||
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Function / homology | ![]() dopamine neurotransmitter receptor activity, coupled via Gs / dopamine neurotransmitter receptor activity / cerebral cortex GABAergic interneuron migration / Dopamine receptors / operant conditioning / regulation of dopamine uptake involved in synaptic transmission / modification of postsynaptic structure / dopamine binding / heterotrimeric G-protein binding / peristalsis ...dopamine neurotransmitter receptor activity, coupled via Gs / dopamine neurotransmitter receptor activity / cerebral cortex GABAergic interneuron migration / Dopamine receptors / operant conditioning / regulation of dopamine uptake involved in synaptic transmission / modification of postsynaptic structure / dopamine binding / heterotrimeric G-protein binding / peristalsis / regulation of dopamine metabolic process / G protein-coupled receptor complex / sensitization / phospholipase C-activating dopamine receptor signaling pathway / grooming behavior / dopamine transport / positive regulation of neuron migration / habituation / astrocyte development / positive regulation of potassium ion transport / striatum development / conditioned taste aversion / dentate gyrus development / maternal behavior / arrestin family protein binding / non-motile cilium / adult walking behavior / long-term synaptic depression / mating behavior / 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 / neuronal action potential / developmental growth / G-protein alpha-subunit binding / D1 dopamine receptor binding / intracellular transport / GABA-ergic synapse / behavioral fear response / Hedgehog 'off' state / prepulse inhibition / adenylate cyclase-activating adrenergic receptor signaling pathway / activation of adenylate cyclase activity / synapse assembly / response to amphetamine / 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 / 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-coupled acetylcholine receptor signaling pathway / G-protein activation / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / cilium / Prostacyclin signalling through prostacyclin receptor / Glucagon signaling in metabolic regulation / G beta:gamma signalling through CDC42 / memory / cognition / platelet aggregation / 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 / photoreceptor disc membrane / 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 / vasodilation / 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 / protein import into nucleus Similarity search - Function | |||||||||
Biological species | ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 4.16 Å | |||||||||
![]() | Xiao T / Zheng S | |||||||||
Funding support | ![]()
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![]() | ![]() 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 | ![]() | 20.8 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 15.2 KB 15.2 KB | Display Display | ![]() |
Images | ![]() | 23.9 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7f24MC ![]() 7f0tC ![]() 7f1oC ![]() 7f1zC ![]() 7f23C M: atomic model generated by this map C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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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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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
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Sample components
-Entire : Cryo-EM structure of the GTP-bound dopamine receptor 1 and mini-G...
Entire | Name: Cryo-EM structure of the GTP-bound dopamine receptor 1 and mini-Gs complex without Nb35 |
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Components |
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-Supramolecule #1: Cryo-EM structure of the GTP-bound dopamine receptor 1 and mini-G...
Supramolecule | Name: Cryo-EM structure of the GTP-bound dopamine receptor 1 and mini-Gs complex without Nb35 type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#4 |
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Source (natural) | Organism: ![]() |
Recombinant expression | Organism: ![]() |
-Macromolecule #1: 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: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 28.907684 KDa |
Recombinant expression | Organism: ![]() |
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 #2: D(1A) dopamine receptor
Macromolecule | Name: D(1A) dopamine receptor / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 52.409656 KDa |
Recombinant expression | Organism: ![]() |
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 #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: 39.418086 KDa |
Recombinant expression | Organism: ![]() |
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: ![]() |
Molecular weight | Theoretical: 7.845078 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MASNNTASIA QARKLVEQLK MEANIDRIKV SKAAADLMAY CEAHAKEDPL LTPVPASENP FREKKFFSAI L |
-Macromolecule #5: GUANOSINE-5'-TRIPHOSPHATE
Macromolecule | Name: GUANOSINE-5'-TRIPHOSPHATE / type: ligand / ID: 5 / Number of copies: 1 / Formula: GTP |
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Molecular weight | Theoretical: 523.18 Da |
Chemical component information | ![]() ChemComp-GTP: |
-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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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Concentration | 4.0 mg/mL |
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Buffer | pH: 7.5 |
Grid | Model: Quantifoil R1.2/1.3 / Support film - Material: CARBON / Support film - topology: HOLEY |
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 281 K / Instrument: FEI VITROBOT MARK IV |
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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: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal magnification: 64000 |
Sample stage | Cooling holder cryogen: NITROGEN |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |