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Yorodumi- EMDB-44866: Global reconstruction of DRD2 bound to LSD in complex with a mini... -
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Basic information
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| Title | Global reconstruction of DRD2 bound to LSD in complex with a mini-GoA and scFv16 obtained by cryo-electron microscopy (cryoEM) | |||||||||
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Keywords | GPCR / G-protein Coupled Receptor / DRD2 / serotonin / psychedelics / MEMBRANE PROTEIN | |||||||||
| Function / homology | Function and homology informationnegative regulation of dopamine receptor signaling pathway / positive regulation of dopamine uptake involved in synaptic transmission / negative regulation of dephosphorylation / 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 / negative regulation of circadian sleep/wake cycle, sleep / 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 / 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 / negative regulation of circadian sleep/wake cycle, sleep / regulation of synapse structural plasticity / regulation of locomotion involved in locomotory behavior / neuron-neuron synaptic transmission / negative regulation of dopamine secretion / adenohypophysis development / negative regulation of cellular response to hypoxia / hyaloid vascular plexus regression / adenylate cyclase-inhibiting dopamine receptor signaling pathway / cerebral cortex GABAergic interneuron migration / response to inactivity / orbitofrontal cortex development / regulation of potassium ion transport / Dopamine receptors / 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 / positive regulation of growth hormone secretion / peristalsis / heterotrimeric G-protein binding / drinking behavior / G protein-coupled receptor complex / grooming behavior / behavioral response to ethanol / positive regulation of renal sodium excretion / auditory behavior / striatum development / positive regulation of G protein-coupled receptor signaling pathway / dopaminergic synapse / mu-type opioid receptor binding / corticotropin-releasing hormone receptor 1 binding / positive regulation of multicellular organism growth / G protein-coupled receptor internalization / non-motile cilium / heterocyclic compound binding / vesicle docking involved in exocytosis / response to iron ion / G protein-coupled dopamine receptor signaling pathway / negative regulation of synaptic transmission, glutamatergic / positive regulation of urine volume / adult walking behavior / arachidonate secretion / ciliary membrane / negative regulation of cytosolic calcium ion concentration / positive regulation of neuroblast proliferation / response to morphine / regulation of synaptic transmission, GABAergic / temperature homeostasis / positive regulation of cytokinesis / regulation of heart contraction / pigmentation / dopamine metabolic process / dopamine uptake involved in synaptic transmission / parallel fiber to Purkinje cell synapse / regulation of dopamine secretion / positive regulation of receptor internalization / cellular response to ethanol / response to light stimulus / lateral plasma membrane / associative learning / neuroblast proliferation / G-protein alpha-subunit binding / negative regulation of protein secretion / endocytic vesicle / prepulse inhibition / potassium channel regulator activity / long-term memory / sperm flagellum / response to axon injury / postsynaptic modulation of chemical synaptic transmission / negative regulation of blood pressure / regulation of sodium ion transport / behavioral response to cocaine / cellular response to retinoic acid / synapse assembly / release of sequestered calcium ion into cytosol / ionotropic glutamate receptor binding / G protein-coupled serotonin receptor binding / adenylate cyclase regulator activity / adenylate cyclase-inhibiting serotonin receptor signaling pathway / presynaptic modulation of chemical synaptic transmission / negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / axon terminus / acrosomal vesicle / axonogenesis / regulation of heart rate / negative regulation of innate immune response / muscle contraction / negative regulation of cell migration / epithelial cell proliferation Similarity search - Function | |||||||||
| Biological species | Homo sapiens (human) / ![]() | |||||||||
| Method | single particle reconstruction / cryo EM / Resolution: 2.32 Å | |||||||||
Authors | Kim K / Gumpper RH / Fay JF / Roth BL | |||||||||
| Funding support | United States, 1 items
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Citation | Journal: Neuron / Year: 2025Title: The polypharmacology of psychedelics reveals multiple targets for potential therapeutics. Authors: Manish K Jain / Ryan H Gumpper / Samuel T Slocum / Gavin P Schmitz / Jakob S Madsen / Tia A Tummino / Carl-Mikael Suomivuori / Xi-Ping Huang / Laura Shub / Jeffrey F DiBerto / Kuglae Kim / ...Authors: Manish K Jain / Ryan H Gumpper / Samuel T Slocum / Gavin P Schmitz / Jakob S Madsen / Tia A Tummino / Carl-Mikael Suomivuori / Xi-Ping Huang / Laura Shub / Jeffrey F DiBerto / Kuglae Kim / Chelsea DeLeon / Brain E Krumm / Jonathan F Fay / Michael Keiser / Alexander S Hauser / Ron O Dror / Brian Shoichet / David E Gloriam / David E Nichols / Bryan L Roth / ![]() Abstract: The classical psychedelics (+)-lysergic acid diethylamide (LSD), psilocybin, and mescaline exert their psychedelic effects via activation of the 5-HT serotonin receptor (5-HTR). Recent clinical ...The classical psychedelics (+)-lysergic acid diethylamide (LSD), psilocybin, and mescaline exert their psychedelic effects via activation of the 5-HT serotonin receptor (5-HTR). Recent clinical studies have suggested that classical psychedelics may additionally have therapeutic potential for many neuropsychiatric conditions including depression, anxiety, migraine and cluster headaches, drug abuse, and post-traumatic stress disorder. In this study, we investigated the pharmacology of 41 classical psychedelics from the tryptamine, phenethylamine, and lysergamide chemical classes. We profiled these compounds against 318 human G-protein-coupled receptors (GPCRs) to elucidate their target profiles, and in the case of LSD, against more than 450 human kinases. We found that psychedelics have potent and efficacious actions at nearly every serotonin, dopamine, and adrenergic receptor. We quantified their activation for multiple transducers and found that psychedelics stimulate multiple 5-HTR transducers, each of which correlates with psychedelic drug-like actions in vivo. Our results suggest that multiple molecular targets likely contribute to the actions of psychedelics. | |||||||||
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Structure visualization
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Downloads & links
-EMDB archive
| Map data | emd_44866.map.gz | 85.2 MB | EMDB map data format | |
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| Header (meta data) | emd-44866-v30.xml emd-44866.xml | 23.1 KB 23.1 KB | Display Display | EMDB header |
| Images | emd_44866.png | 54.5 KB | ||
| Masks | emd_44866_msk_1.map | 91.1 MB | Mask map | |
| Filedesc metadata | emd-44866.cif.gz | 7.4 KB | ||
| Others | emd_44866_half_map_1.map.gz emd_44866_half_map_2.map.gz | 84.5 MB 84.5 MB | ||
| Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-44866 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-44866 | HTTPS FTP |
-Related structure data
| Related structure data | ![]() 9bsbMC ![]() 9bs9C M: atomic model generated by this map C: citing same article ( |
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| Similar structure data | Similarity search - Function & homology F&H Search |
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Links
| EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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| Related items in Molecule of the Month |
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Map
| File | Download / File: emd_44866.map.gz / Format: CCP4 / Size: 91.1 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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| Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
| Voxel size | X=Y=Z: 0.88 Å | ||||||||||||||||||||||||||||||||||||
| Density |
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| Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
| Details | EMDB XML:
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-Supplemental data
-Mask #1
| File | emd_44866_msk_1.map | ||||||||||||
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-Half map: #2
| File | emd_44866_half_map_1.map | ||||||||||||
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| Density Histograms |
-Half map: #1
| File | emd_44866_half_map_2.map | ||||||||||||
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Sample components
-Entire : DRD2 in complex mini-GoA
| Entire | Name: DRD2 in complex mini-GoA |
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| Components |
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-Supramolecule #1: DRD2 in complex mini-GoA
| Supramolecule | Name: DRD2 in complex mini-GoA / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #3, #1-#2, #4-#5 |
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| Source (natural) | Organism: Homo sapiens (human) |
-Macromolecule #1: 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: 1 / Number of copies: 1 / Enantiomer: LEVO |
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| Source (natural) | Organism: Homo sapiens (human) |
| 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 #2: 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: 2 / Number of copies: 1 / Enantiomer: LEVO |
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| Source (natural) | Organism: Homo sapiens (human) |
| 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 #3: Soluble cytochrome b562,D(2) dopamine receptor
| Macromolecule | Name: Soluble cytochrome b562,D(2) dopamine receptor / 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: 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 #4: Single chain Fab 16 (scFv16)
| Macromolecule | Name: Single chain Fab 16 (scFv16) / type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO |
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| Source (natural) | Organism: ![]() |
| Molecular weight | Theoretical: 28.674902 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 H |
-Macromolecule #5: Guanine nucleotide-binding protein G(o) subunit alpha
| Macromolecule | Name: Guanine nucleotide-binding protein G(o) subunit alpha / 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: 40.22157 KDa |
| Recombinant expression | Organism: ![]() |
| Sequence | String: MGCTLSAEDK AAVERSKMIE KNLKEDGISA AKDVKLLLLG ADNSGKSTIV KQMKIIHEDG FSGEDVKQYK PVVYSNTIQS LAAIVRAMD TLGIEYGDKE RKADAKMVCD VVSRMEDTEP FSAELLSAMM RLWGDSGIQE CFNRSREYQL NDSAKYYLDS L DRIGAADY ...String: MGCTLSAEDK AAVERSKMIE KNLKEDGISA AKDVKLLLLG ADNSGKSTIV KQMKIIHEDG FSGEDVKQYK PVVYSNTIQS LAAIVRAMD TLGIEYGDKE RKADAKMVCD VVSRMEDTEP FSAELLSAMM RLWGDSGIQE CFNRSREYQL NDSAKYYLDS L DRIGAADY QPTEQDILRT RVKTTGIVET HFTFKNLHFR LFDVGGQRSE RKKWIHCFED VTAIIFCVDL SDYDQVLHED ET TNRMHES LMLFDSICNN KFFIDTSIIL FLNKKDLFGE KIKKSPLTIC FPEYTGPNTY EDAAAYIQAQ FESKNRSPNK EIY CHMTCA TDTNNAQVIF DAVTDIIIAN NLRGCGLY UniProtKB: Guanine nucleotide-binding protein G(o) subunit alpha |
-Macromolecule #6: (8alpha)-N,N-diethyl-6-methyl-9,10-didehydroergoline-8-carboxamide
| Macromolecule | Name: (8alpha)-N,N-diethyl-6-methyl-9,10-didehydroergoline-8-carboxamide type: ligand / ID: 6 / Number of copies: 1 / Formula: 7LD |
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| Molecular weight | Theoretical: 323.432 Da |
| Chemical component information | ![]() ChemComp-7LD: |
-Experimental details
-Structure determination
| Method | cryo EM |
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Processing | single particle reconstruction |
| Aggregation state | particle |
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Sample preparation
| Buffer | pH: 7.4 |
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| Vitrification | Cryogen name: ETHANE-PROPANE |
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Electron microscopy
| Microscope | FEI TALOS ARCTICA |
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| Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 49.5 e/Å2 |
| Electron beam | Acceleration voltage: 200 kV / Electron source: FIELD EMISSION GUN |
| Electron optics | Illumination mode: OTHER / Imaging mode: OTHER / Nominal defocus max: 2.6 µm / Nominal defocus min: 0.17 µm |
| Experimental equipment | ![]() Model: Talos Arctica / Image courtesy: FEI Company |
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About Yorodumi



Keywords
Homo sapiens (human)
Authors
United States, 1 items
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Processing
FIELD EMISSION GUN

