+Open data
-Basic information
Entry | Database: PDB / ID: 8aw2 | ||||||
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Title | Mouse serotonin 5-HT3A receptor in complex with vortioxetine | ||||||
Components | 5-hydroxytryptamine receptor 3A | ||||||
Keywords | MEMBRANE PROTEIN / Pentameric ligand-gated ion channel / Serotonin receptor / vortioxetine | ||||||
Function / homology | Function and homology information Neurotransmitter receptors and postsynaptic signal transmission / serotonin-gated monoatomic cation channel activity / serotonin-activated cation-selective channel complex / serotonin receptor signaling pathway / serotonin binding / inorganic cation transmembrane transport / acetylcholine-gated monoatomic cation-selective channel activity / cleavage furrow / ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential / presynaptic membrane ...Neurotransmitter receptors and postsynaptic signal transmission / serotonin-gated monoatomic cation channel activity / serotonin-activated cation-selective channel complex / serotonin receptor signaling pathway / serotonin binding / inorganic cation transmembrane transport / acetylcholine-gated monoatomic cation-selective channel activity / cleavage furrow / ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential / presynaptic membrane / postsynaptic membrane / neuron projection / axon / neuronal cell body / glutamatergic synapse / synapse / identical protein binding Similarity search - Function | ||||||
Biological species | Mus musculus (house mouse) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.01 Å | ||||||
Authors | Lopez-Sanchez, U. / Nury, H. | ||||||
Funding support | European Union, 1items
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Citation | Journal: Nat Struct Mol Biol / Year: 2024 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 Grønborg 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
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8aw2.cif.gz | 567.5 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8aw2.ent.gz | 383.3 KB | Display | PDB format |
PDBx/mmJSON format | 8aw2.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/aw/8aw2 ftp://data.pdbj.org/pub/pdb/validation_reports/aw/8aw2 | HTTPS FTP |
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-Related structure data
Related structure data | 15689MC 8axdC 8bl8C 8blaC 8blbC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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Noncrystallographic symmetry (NCS) | NCS domain:
NCS domain segments:
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