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- EMDB-16103: Human serotonin 5-HT3A receptor (apo, active/distorted conformation) -
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Open data
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Basic information
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Title | Human serotonin 5-HT3A receptor (apo, active/distorted conformation) | |||||||||
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![]() | Human pentameric ligand-gated ion channel / Human serotonin receptor / MEMBRANE PROTEIN | |||||||||
Function / homology | ![]() Neurotransmitter receptors and postsynaptic signal transmission / serotonin-gated monoatomic cation channel activity / serotonin-activated cation-selective channel complex / serotonin receptor signaling pathway / excitatory extracellular ligand-gated monoatomic ion channel activity / serotonin binding / inorganic cation transmembrane transport / acetylcholine-gated monoatomic cation-selective channel activity / cleavage furrow / transmembrane transporter complex ...Neurotransmitter receptors and postsynaptic signal transmission / serotonin-gated monoatomic cation channel activity / serotonin-activated cation-selective channel complex / serotonin receptor signaling pathway / excitatory extracellular ligand-gated monoatomic ion channel activity / serotonin binding / inorganic cation transmembrane transport / acetylcholine-gated monoatomic cation-selective channel activity / cleavage furrow / transmembrane transporter complex / ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential / transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential / postsynaptic membrane / neuron projection / synapse / identical protein binding / plasma membrane Similarity search - Function | |||||||||
Biological species | ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.21 Å | |||||||||
![]() | Lopez-Sanchez U / Nury H | |||||||||
Funding support | European Union, 1 items
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![]() | ![]() Title: Structural determinants for activity of the antidepressant vortioxetine at human and rodent 5-HT receptors. Authors: Uriel López-Sánchez / Lachlan Jake Munro / Lucy Kate Ladefoged / Anders Juel Pedersen / Christian Colding Brun / Signe Meisner Lyngby / Delphine Baud / Céline Juillan-Binard / Miriam ...Authors: Uriel López-Sánchez / Lachlan Jake Munro / Lucy Kate Ladefoged / Anders Juel Pedersen / Christian Colding Brun / Signe Meisner Lyngby / Delphine Baud / Céline Juillan-Binard / Miriam Grønlund Pedersen / Sarah C R Lummis / Benny Bang-Andersen / Birgit Schiøtt / Christophe Chipot / Guy Schoehn / Jacques Neyton / Francois Dehez / Hugues Nury / Anders S Kristensen / ![]() ![]() ![]() ![]() Abstract: Vortioxetine (VTX) is a recently approved antidepressant that targets a variety of serotonin receptors. Here, we investigate the drug's molecular mechanism of operation at the serotonin 5-HT receptor ...Vortioxetine (VTX) is a recently approved antidepressant that targets a variety of serotonin receptors. Here, we investigate the drug's molecular mechanism of operation at the serotonin 5-HT receptor (5-HTR), which features two properties: VTX acts differently on rodent and human 5-HTR, and VTX appears to suppress any subsequent response to agonists. Using a combination of cryo-EM, electrophysiology, voltage-clamp fluorometry and molecular dynamics, we show that VTX stabilizes a resting inhibited state of the mouse 5-HTR and an agonist-bound-like state of human 5-HTR, in line with the functional profile of the drug. We report four human 5-HTR structures and show that the human receptor transmembrane domain is intrinsically fragile. We also explain the lack of recovery after VTX administration via a membrane partition mechanism. | |||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 59.5 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 14.8 KB 14.8 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 8.4 KB | Display | ![]() |
Images | ![]() | 73.3 KB | ||
Masks | ![]() | 64 MB | ![]() | |
Filedesc metadata | ![]() | 5.8 KB | ||
Others | ![]() ![]() | 59.3 MB 59.3 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8bl8MC ![]() 8aw2C ![]() 8axdC ![]() 8blaC ![]() 8blbC 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: 1.145 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Mask #1
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-Half map: #2
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Density Histograms |
-Half map: #1
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Density Histograms |
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Sample components
-Entire : Human serotonin 5-HT3A receptor
Entire | Name: Human serotonin 5-HT3A receptor |
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Components |
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-Supramolecule #1: Human serotonin 5-HT3A receptor
Supramolecule | Name: Human serotonin 5-HT3A receptor / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1 / Details: apo, active/disorted conformation |
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Source (natural) | Organism: ![]() |
-Macromolecule #1: 5-hydroxytryptamine receptor 3A
Macromolecule | Name: 5-hydroxytryptamine receptor 3A / type: protein_or_peptide / ID: 1 / Number of copies: 5 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 46.386031 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: TTRPALLRLS DYLLTNYRKG VRPVRDWRKP TTVSIDVIVY AILNVDEKNQ VLTTYIWYRQ YWTDEFLQWN PEDFDNITKL SIPTDSIWV PDILINEFVD VGKSPNIPYV YIRHQGEVQN YKPLQVVTAC SLDIYNFPFD VQNCSLTFTS WLHTIQDINI S LWRLPEKV ...String: TTRPALLRLS DYLLTNYRKG VRPVRDWRKP TTVSIDVIVY AILNVDEKNQ VLTTYIWYRQ YWTDEFLQWN PEDFDNITKL SIPTDSIWV PDILINEFVD VGKSPNIPYV YIRHQGEVQN YKPLQVVTAC SLDIYNFPFD VQNCSLTFTS WLHTIQDINI S LWRLPEKV KSDRSVFMNQ GEWELLGVLP YFREFSMESS NYYAEMKFYV VIRRRPLFYV VSLLLPSIFL MVMDIVGFYL PP NSGERVS FKITLLLGYS VFLIIVSDTL PATAIGTPLI GVYFVVCMAL LVISLAETIF IVRLVHKQDL QQPVPAWLRH LVL ERIAWL LCLASLAVCG LLQELSSIRQ FLEKRDEIRE VARDWLRVGS VLDKLLFHIY LLAVLAYSIT LVMLWSIWQY A UniProtKB: 5-hydroxytryptamine receptor 3A, 5-hydroxytryptamine receptor 3A |
-Macromolecule #3: 2-acetamido-2-deoxy-beta-D-glucopyranose
Macromolecule | Name: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 3 / Number of copies: 5 / Formula: NAG |
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Molecular weight | Theoretical: 221.208 Da |
Chemical component information | ![]() ChemComp-NAG: |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Concentration | 6.0 mg/mL |
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Buffer | pH: 7.4 |
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 279 K / Instrument: FEI VITROBOT MARK IV |
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Electron microscopy
Microscope | TFS GLACIOS |
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Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: COUNTING / Average electron dose: 40.0 e/Å2 |
Electron beam | Acceleration voltage: 200 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.3000000000000003 µm / Nominal defocus min: 0.7000000000000001 µm |