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Yorodumi- EMDB-25401: 5-HT2B receptor bound to LSD obtained by cryo-electron microscopy... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-25401 | |||||||||
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Title | 5-HT2B receptor bound to LSD obtained by cryo-electron microscopy (cryoEM) | |||||||||
Map data | Cryo-EM map for 5-HT2BR bound to LSD | |||||||||
Sample |
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Function / homology | Function and homology information intestine smooth muscle contraction / G protein-coupled serotonin receptor complex / Gq/11-coupled serotonin receptor activity / phospholipase C-activating serotonin receptor signaling pathway / positive regulation of phosphatidylinositol biosynthetic process / G protein-coupled serotonin receptor signaling pathway / protein kinase C signaling / regulation of behavior / Serotonin receptors / serotonin receptor signaling pathway ...intestine smooth muscle contraction / G protein-coupled serotonin receptor complex / Gq/11-coupled serotonin receptor activity / phospholipase C-activating serotonin receptor signaling pathway / positive regulation of phosphatidylinositol biosynthetic process / G protein-coupled serotonin receptor signaling pathway / protein kinase C signaling / regulation of behavior / Serotonin receptors / serotonin receptor signaling pathway / : / embryonic morphogenesis / cellular response to temperature stimulus / serotonin binding / G protein-coupled receptor internalization / vasoconstriction / G protein-coupled serotonin receptor activity / : / cardiac muscle hypertrophy / neural crest cell differentiation / neural crest cell migration / neurotransmitter receptor activity / cGMP-mediated signaling / G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / positive regulation of cell division / G-protein alpha-subunit binding / heart morphogenesis / release of sequestered calcium ion into cytosol / phosphorylation / positive regulation of endothelial cell proliferation / ERK1 and ERK2 cascade / phosphatidylinositol 3-kinase/protein kinase B signal transduction / GTPase activator activity / positive regulation of nitric-oxide synthase activity / positive regulation of cytokine production / calcium-mediated signaling / positive regulation of MAP kinase activity / intracellular calcium ion homeostasis / G alpha (q) signalling events / chemical synaptic transmission / positive regulation of canonical NF-kappaB signal transduction / positive regulation of ERK1 and ERK2 cascade / response to xenobiotic stimulus / G protein-coupled receptor signaling pathway / dendrite / positive regulation of cell population proliferation / synapse / negative regulation of apoptotic process / nucleoplasm / plasma membrane / cytoplasm Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.7 Å | |||||||||
Authors | Barros-Alvarez X / Cao C / Panova O / Roth BL / Skiniotis G | |||||||||
Funding support | 1 items
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Citation | Journal: Neuron / Year: 2022 Title: Signaling snapshots of a serotonin receptor activated by the prototypical psychedelic LSD. Authors: Can Cao / Ximena Barros-Álvarez / Shicheng Zhang / Kuglae Kim / Marc A Dämgen / Ouliana Panova / Carl-Mikael Suomivuori / Jonathan F Fay / Xiaofang Zhong / Brian E Krumm / Ryan H Gumpper / ...Authors: Can Cao / Ximena Barros-Álvarez / Shicheng Zhang / Kuglae Kim / Marc A Dämgen / Ouliana Panova / Carl-Mikael Suomivuori / Jonathan F Fay / Xiaofang Zhong / Brian E Krumm / Ryan H Gumpper / Alpay B Seven / Michael J Robertson / Nevan J Krogan / Ruth Hüttenhain / David E Nichols / Ron O Dror / Georgios Skiniotis / Bryan L Roth / Abstract: Serotonin (5-hydroxytryptamine [5-HT]) 5-HT2-family receptors represent essential targets for lysergic acid diethylamide (LSD) and all other psychedelic drugs. Although the primary psychedelic drug ...Serotonin (5-hydroxytryptamine [5-HT]) 5-HT2-family receptors represent essential targets for lysergic acid diethylamide (LSD) and all other psychedelic drugs. Although the primary psychedelic drug effects are mediated by the 5-HT serotonin receptor (HTR2A), the 5-HT serotonin receptor (HTR2B) has been used as a model receptor to study the activation mechanisms of psychedelic drugs due to its high expression and similarity to HTR2A. In this study, we determined the cryo-EM structures of LSD-bound HTR2B in the transducer-free, Gq-protein-coupled, and β-arrestin-1-coupled states. These structures provide distinct signaling snapshots of LSD's action, ranging from the transducer-free, partially active state to the transducer-coupled, fully active states. Insights from this study will both provide comprehensive molecular insights into the signaling mechanisms of the prototypical psychedelic LSD and accelerate the discovery of novel psychedelic drugs. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_25401.map.gz | 749.5 KB | EMDB map data format | |
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Header (meta data) | emd-25401-v30.xml emd-25401.xml | 12.8 KB 12.8 KB | Display Display | EMDB header |
Images | emd_25401.png | 110.4 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-25401 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-25401 | HTTPS FTP |
-Validation report
Summary document | emd_25401_validation.pdf.gz | 295.3 KB | Display | EMDB validaton report |
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Full document | emd_25401_full_validation.pdf.gz | 294.9 KB | Display | |
Data in XML | emd_25401_validation.xml.gz | 6.6 KB | Display | |
Data in CIF | emd_25401_validation.cif.gz | 7.6 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-25401 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-25401 | HTTPS FTP |
-Related structure data
Related structure data | 7srqMC 7srrC 7srsC 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_25401.map.gz / Format: CCP4 / Size: 178 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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Annotation | Cryo-EM map for 5-HT2BR bound to LSD | ||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 0.8677 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Sample components
-Entire : 5-HT2B receptor bound to LSD
Entire | Name: 5-HT2B receptor bound to LSD |
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Components |
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-Supramolecule #1: 5-HT2B receptor bound to LSD
Supramolecule | Name: 5-HT2B receptor bound to LSD / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1 |
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Source (natural) | Organism: Homo sapiens (human) |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
-Macromolecule #1: 5-hydroxytryptamine receptor 2B
Macromolecule | Name: 5-hydroxytryptamine receptor 2B / 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: 35.052629 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
Sequence | String: TESIPEEMKQ IVEEQGNKLH WAALLILMVI IPTIGGNTLV ILAVSLEKKL QYATNYFLMS LAVADLLVGL FVMPIALLTI MFEAMWPLP LVLCPAWLFL DVLFSTASIW HLCAISVDRY IAIKKPIQAN QYNSRATAFI KITVVWLISI GIAIPVPIKG I ETDVDNPN ...String: TESIPEEMKQ IVEEQGNKLH WAALLILMVI IPTIGGNTLV ILAVSLEKKL QYATNYFLMS LAVADLLVGL FVMPIALLTI MFEAMWPLP LVLCPAWLFL DVLFSTASIW HLCAISVDRY IAIKKPIQAN QYNSRATAFI KITVVWLISI GIAIPVPIKG I ETDVDNPN NITCVLTKER FGDFMLFGSL AAFFTPLAIM IVTYFLTIHA LQKVRLLSGS RQTISNEQRA SKVLGIVFFL FL LMWCPFF ITNITLVLCD SCNQTTLQML LEIFVWIGYV SSGVNPLVYT LFNKTFRDAF GRYITCNYRA TKSV |
-Macromolecule #2: 2-acetamido-2-deoxy-beta-D-glucopyranose
Macromolecule | Name: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 2 / Number of copies: 1 / Formula: NAG |
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Molecular weight | Theoretical: 221.208 Da |
Chemical component information | ChemComp-NAG: |
-Macromolecule #3: (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: 3 / 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 |
-Sample preparation
Concentration | 6.5 mg/mL |
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Buffer | pH: 7.5 |
Grid | Model: UltrAuFoil R1.2/1.3 |
Vitrification | Cryogen name: ETHANE / 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: 1.23 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | C2 aperture diameter: 70.0 µm / Calibrated magnification: 55000 / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 1.8 µm / Nominal defocus min: 0.8 µm |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |