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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 / nervous system process involved in regulation of systemic arterial blood pressure / negative regulation of dephosphorylation / positive regulation of glial cell-derived neurotrophic factor production / adenohypophysis development / acid secretion / regulation of synapse structural plasticity / dopamine neurotransmitter receptor activity, coupled via Gi/Go / response to histamine ...negative regulation of dopamine receptor signaling pathway / positive regulation of dopamine uptake involved in synaptic transmission / nervous system process involved in regulation of systemic arterial blood pressure / negative regulation of dephosphorylation / positive regulation of glial cell-derived neurotrophic factor production / adenohypophysis development / acid secretion / regulation of synapse structural plasticity / dopamine neurotransmitter receptor activity, coupled via Gi/Go / response to histamine / negative regulation of circadian sleep/wake cycle, sleep / regulation of locomotion involved in locomotory behavior / neuron-neuron synaptic transmission / regulation of potassium ion transport / negative regulation of cellular response to hypoxia / negative regulation of dopamine secretion / adenylate cyclase-inhibiting dopamine receptor signaling pathway / response to inactivity / cerebral cortex GABAergic interneuron migration / orbitofrontal cortex development / hyaloid vascular plexus regression / Dopamine receptors / branching morphogenesis of a nerve / peristalsis / regulation of dopamine uptake involved in synaptic transmission / dopamine binding / phospholipase C-activating dopamine receptor signaling pathway / positive regulation of growth hormone secretion / heterotrimeric G-protein binding / G protein-coupled receptor complex / beta-arrestin-dependent dopamine receptor signaling pathway / striatum development / drinking behavior / auditory behavior / adult walking behavior / positive regulation of G protein-coupled receptor signaling pathway / dopaminergic synapse / mu-type opioid receptor binding / corticotropin-releasing hormone receptor 1 binding / behavioral response to ethanol / non-motile cilium / G protein-coupled receptor internalization / positive regulation of neuroblast proliferation / negative regulation of synaptic transmission, glutamatergic / response to iron ion / G protein-coupled dopamine receptor signaling pathway / arachidonate secretion / ciliary membrane / response to morphine / positive regulation of cytokinesis / regulation of synaptic transmission, GABAergic / negative regulation of cytosolic calcium ion concentration / regulation of sodium ion transport / dopamine metabolic process / temperature homeostasis / parallel fiber to Purkinje cell synapse / regulation of dopamine secretion / associative learning / response to axon injury / positive regulation of receptor internalization / lateral plasma membrane / negative regulation of protein secretion / negative regulation of insulin secretion / response to light stimulus / cellular response to ethanol / potassium channel regulator activity / endocytic vesicle / G-protein alpha-subunit binding / prepulse inhibition / sperm flagellum / postsynaptic modulation of chemical synaptic transmission / long-term memory / cellular response to retinoic acid / negative regulation of blood pressure / release of sequestered calcium ion into cytosol / axonogenesis / behavioral response to cocaine / muscle contraction / synapse assembly / presynaptic modulation of chemical synaptic transmission / regulation of heart rate / negative regulation of innate immune response / response to amphetamine / ionotropic glutamate receptor binding / acrosomal vesicle / adenylate cyclase-inhibiting serotonin receptor signaling pathway / negative regulation of cell migration / G protein-coupled serotonin receptor binding / excitatory postsynaptic potential / axon terminus / negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / locomotory behavior / positive regulation of long-term synaptic potentiation / response to nicotine / response to cocaine / circadian regulation of gene expression / electron transport chain / regulation of long-term neuronal synaptic plasticity / visual learning / intracellular calcium ion homeostasis 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

