+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-35683 | |||||||||
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Title | Dopamine Receptor D1R-Gs-Rotigotine complex | |||||||||
Map data | ||||||||||
Sample |
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Keywords | Dopamine / Dopamine receptor / GPCR / D1R / Gs / Rotigotine / Parkinson's disease / Restless legs syndrome / MEMBRANE PROTEIN | |||||||||
Function / homology | Function and homology information 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 / behavioral response to cocaine / G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / neuronal action potential / G-protein alpha-subunit binding / GABA-ergic synapse / behavioral fear response / positive regulation of synaptic transmission, glutamatergic / prepulse inhibition / adenylate cyclase-activating adrenergic receptor signaling pathway / activation of adenylate cyclase activity / synapse assembly / response to amphetamine / presynaptic modulation of chemical synaptic transmission / positive regulation of release of sequestered calcium ion into cytosol / synaptic transmission, glutamatergic / G protein-coupled receptor activity / long-term synaptic potentiation / regulation of protein phosphorylation / visual learning / Olfactory Signaling Pathway / Activation of the phototransduction cascade / vasodilation / 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 / 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 / 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 / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / GPER1 signaling / G-protein beta-subunit binding / Inactivation, recovery and regulation of the phototransduction cascade / heterotrimeric G-protein complex / G alpha (12/13) signalling events / extracellular vesicle / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / GTPase binding / retina development in camera-type eye / Ca2+ pathway Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) / Lama glama (llama) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.2 Å | |||||||||
Authors | Xu P / Huang S / Zhuang Y / Mao C / Zhang Y / Wang Y / Li H / Jiang Y / Xu HE | |||||||||
Funding support | China, 1 items
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Citation | Journal: Cell Res / Year: 2023 Title: Structural genomics of the human dopamine receptor system. Authors: Peiyu Xu / Sijie Huang / Brian E Krumm / Youwen Zhuang / Chunyou Mao / Yumu Zhang / Yue Wang / Xi-Ping Huang / Yong-Feng Liu / Xinheng He / Huadong Li / Wanchao Yin / Yi Jiang / Yan Zhang / ...Authors: Peiyu Xu / Sijie Huang / Brian E Krumm / Youwen Zhuang / Chunyou Mao / Yumu Zhang / Yue Wang / Xi-Ping Huang / Yong-Feng Liu / Xinheng He / Huadong Li / Wanchao Yin / Yi Jiang / Yan Zhang / Bryan L Roth / H Eric Xu / Abstract: The dopaminergic system, including five dopamine receptors (D1R to D5R), plays essential roles in the central nervous system (CNS); and ligands that activate dopamine receptors have been used to ...The dopaminergic system, including five dopamine receptors (D1R to D5R), plays essential roles in the central nervous system (CNS); and ligands that activate dopamine receptors have been used to treat many neuropsychiatric disorders, including Parkinson's Disease (PD) and schizophrenia. Here, we report cryo-EM structures of all five subtypes of human dopamine receptors in complex with G protein and bound to the pan-agonist, rotigotine, which is used to treat PD and restless legs syndrome. The structures reveal the basis of rotigotine recognition in different dopamine receptors. Structural analysis together with functional assays illuminate determinants of ligand polypharmacology and selectivity. The structures also uncover the mechanisms of dopamine receptor activation, unique structural features among the five receptor subtypes, and the basis of G protein coupling specificity. Our work provides a comprehensive set of structural templates for the rational design of specific ligands to treat CNS diseases targeting the dopaminergic system. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_35683.map.gz | 55.7 MB | EMDB map data format | |
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Header (meta data) | emd-35683-v30.xml emd-35683.xml | 19.9 KB 19.9 KB | Display Display | EMDB header |
Images | emd_35683.png | 85.2 KB | ||
Filedesc metadata | emd-35683.cif.gz | 6.6 KB | ||
Others | emd_35683_half_map_1.map.gz emd_35683_half_map_2.map.gz | 24.3 MB 24.3 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-35683 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-35683 | HTTPS FTP |
-Validation report
Summary document | emd_35683_validation.pdf.gz | 849.5 KB | Display | EMDB validaton report |
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Full document | emd_35683_full_validation.pdf.gz | 849.1 KB | Display | |
Data in XML | emd_35683_validation.xml.gz | 11.3 KB | Display | |
Data in CIF | emd_35683_validation.cif.gz | 12.9 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-35683 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-35683 | HTTPS FTP |
-Related structure data
Related structure data | 8irrMC 8irsC 8irtC 8iruC 8irvC 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_35683.map.gz / Format: CCP4 / Size: 59.6 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Voxel size | X=Y=Z: 0.8 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: #1
File | emd_35683_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #2
File | emd_35683_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
-Entire : Dopamine Receptor D1R-Gs-Rotigotine complex
Entire | Name: Dopamine Receptor D1R-Gs-Rotigotine complex |
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Components |
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-Supramolecule #1: Dopamine Receptor D1R-Gs-Rotigotine complex
Supramolecule | Name: Dopamine Receptor D1R-Gs-Rotigotine complex / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#5 |
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Source (natural) | Organism: Homo sapiens (human) |
-Macromolecule #1: Guanine nucleotide-binding protein G(s) subunit alpha isoforms short
Macromolecule | Name: 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: Homo sapiens (human) |
Molecular weight | Theoretical: 29.048932 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
Sequence | String: MGCLGNSKTE DQRNEEKAQR EANKMIEKQL QKDKQVYRAT HRLLLLGADN SGKSTIVKQM RIYHVNSGIF ETKFQVDKVN FHMFDVGAQ RDERRKWIQC FNDVTAIIFV VDSSDYNRLQ EALNDFKSIW NNRWLRTISV ILFLNKQDLL AEKVLAGKSK I EDYFPEFA ...String: MGCLGNSKTE DQRNEEKAQR EANKMIEKQL QKDKQVYRAT HRLLLLGADN SGKSTIVKQM RIYHVNSGIF ETKFQVDKVN FHMFDVGAQ RDERRKWIQC FNDVTAIIFV VDSSDYNRLQ EALNDFKSIW NNRWLRTISV ILFLNKQDLL AEKVLAGKSK I EDYFPEFA RYTTPEDATP EPGEDPRVTR AKYFIRDEFL RISTASGDGR HYCYPHFTCS VDTENARRIF NDCRDIIQRM HL RQYELL |
-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: 39.020664 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
Sequence | String: HHHHHHHHMG SLLQSELDQL RQEAEQLKNQ IRDARKACAD ATLSQITNNI DPVGRIQMRT RRTLRGHLAK IYAMHWGTDS RLLVSASQD GKLIIWDSYT TNKVHAIPLR SSWVMTCAYA PSGNYVACGG LDNICSIYNL KTREGNVRVS RELAGHTGYL S CCRFLDDN ...String: HHHHHHHHMG SLLQSELDQL RQEAEQLKNQ IRDARKACAD ATLSQITNNI DPVGRIQMRT RRTLRGHLAK IYAMHWGTDS RLLVSASQD GKLIIWDSYT TNKVHAIPLR SSWVMTCAYA PSGNYVACGG LDNICSIYNL KTREGNVRVS RELAGHTGYL S CCRFLDDN QIVTSSGDTT CALWDIETGQ QTTTFTGHTG DVMSLSLAPD TRLFVSGACD ASAKLWDVRE GMCRQTFTGH ES DINAICF FPNGNAFATG SDDATCRLFD LRADQELMTY SHDNIICGIT SVSFSKSGRL LLAGYDDFNC NVWDALKADR AGV LAGHDN RVSCLGVTDD GMAVATGSWD SFLKIWN UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 |
-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: 7.432554 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
Sequence | String: ASNNTASIAQ ARKLVEQLKM EANIDRIKVS KAAADLMAYC EAHAKEDPLL TPVPASENPF REKKFFC UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 |
-Macromolecule #4: Nanoboy 35
Macromolecule | Name: Nanoboy 35 / type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Lama glama (llama) |
Molecular weight | Theoretical: 14.845516 KDa |
Recombinant expression | Organism: Escherichia coli (E. coli) |
Sequence | String: MQVQLQESGG GLVQPGGSLR LSCAASGFTF SNYKMNWVRQ APGKGLEWVS DISQSGASIS YTGSVKGRFT ISRDNAKNTL YLQMNSLKP EDTAVYYCAR CPAPFTRDCF DVTSTTYAYR GQGTQVTVSS HHHHHH |
-Macromolecule #5: D(1A) dopamine receptor
Macromolecule | Name: D(1A) dopamine receptor / type: protein_or_peptide / ID: 5 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 55.668707 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
Sequence | String: DYKDDDDVDM GQPGNGSAFL LAPNGSHAPD HDVTQQRDEE NLYFQGASMR TLNTSAMDGT GLVVERDFSV RILTACFLSL LILSTLLGN TLVCAAVIRF RHLRSKVTNF FVISLAVSDL LVAVLVMPWK AVAEIAGFWP FGSFCNIWVA FDIMCSTASI L NLCVISVD ...String: DYKDDDDVDM GQPGNGSAFL LAPNGSHAPD HDVTQQRDEE NLYFQGASMR TLNTSAMDGT GLVVERDFSV RILTACFLSL LILSTLLGN TLVCAAVIRF RHLRSKVTNF FVISLAVSDL LVAVLVMPWK AVAEIAGFWP FGSFCNIWVA FDIMCSTASI L NLCVISVD RYWAISSPFR YERKMTPKAA FILISVAWTL SVLISFIPVQ LSWHKAKPTS PSDGNATSLA ETIDNCDSSL SR TYAISSS VISFYIPVAI MIVTYTRIYR IAQKQIRRIA ALERAAVHAK NCQTTTGNGK PVECSQPESS FKMSFKRETK VLK TLSVIM GVFVCCWLPF FILNCILPFC GSGETQPFCI DSNTFDVFVW FGWANSSLNP IIYAFNADFR KAFSTLLGCY RLCP ATNNA IETVSINNNG AAMFSSHHEP RGSISKECNL VYLIPHAVGS SEDLKKEEAA GIARPLEKLS PALSVILDYD TDVSL EKIQ PITQNGQHPT HHHHHHHH UniProtKB: D(1A) dopamine receptor |
-Macromolecule #6: Rotigotine
Macromolecule | Name: Rotigotine / type: ligand / ID: 6 / Number of copies: 1 / Formula: R5F |
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Molecular weight | Theoretical: 315.473 Da |
Chemical component information | ChemComp-R5F: |
-Macromolecule #7: CHOLESTEROL
Macromolecule | Name: CHOLESTEROL / type: ligand / ID: 7 / Number of copies: 3 / Formula: CLR |
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Molecular weight | Theoretical: 386.654 Da |
Chemical component information | ChemComp-CLR: |
-Macromolecule #8: water
Macromolecule | Name: water / type: ligand / ID: 8 / Number of copies: 2 / Formula: HOH |
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Molecular weight | Theoretical: 18.015 Da |
Chemical component information | ChemComp-HOH: |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.3 |
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Vitrification | Cryogen name: ETHANE-PROPANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 (6k x 4k) / Number real images: 6301 / Average electron dose: 60.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 2.2 µm / Nominal defocus min: 1.2 µm |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Startup model | Type of model: EMDB MAP EMDB ID: |
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Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.2 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 448516 |
Initial angle assignment | Type: RANDOM ASSIGNMENT |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |