[English] 日本語
Yorodumi
- EMDB-16105: Human serotonin 5-HT3A receptor in complex with vortioxetine (nan... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-16105
TitleHuman serotonin 5-HT3A receptor in complex with vortioxetine (nanodiscs, ECD, active/distorted conformation)
Map data
Sample
  • Complex: Human 5HT3A receptor in complex with vortioxetine
    • Protein or peptide: 5-hydroxytryptamine receptor 3A
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose
  • Ligand: Vortioxetine
KeywordsHuman pentameric ligand-gated ion channel / Human serotonin receptor / MEMBRANE PROTEIN
Function / homology
Function and homology information


Neurotransmitter receptors and postsynaptic signal transmission / serotonin-gated cation-selective signaling pathway / serotonin-activated cation-selective channel complex / serotonin-gated monoatomic cation channel activity / excitatory extracellular ligand-gated monoatomic ion channel activity / serotonin receptor signaling pathway / transmembrane transporter complex / serotonin binding / : / cleavage furrow ...Neurotransmitter receptors and postsynaptic signal transmission / serotonin-gated cation-selective signaling pathway / serotonin-activated cation-selective channel complex / serotonin-gated monoatomic cation channel activity / excitatory extracellular ligand-gated monoatomic ion channel activity / serotonin receptor signaling pathway / transmembrane transporter complex / serotonin binding / : / cleavage furrow / ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential / regulation of membrane potential / transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential / monoatomic ion transmembrane transport / chemical synaptic transmission / postsynaptic membrane / neuron projection / synapse / identical protein binding / plasma membrane
Similarity search - Function
5-hydroxytryptamine 3 receptor / 5-hydroxytryptamine 3 receptor, A subunit / : / Neurotransmitter-gated ion-channel, conserved site / Neurotransmitter-gated ion-channels signature. / Neurotransmitter-gated ion-channel transmembrane domain / Neurotransmitter-gated ion-channel transmembrane region / Neurotransmitter-gated ion-channel transmembrane domain superfamily / Neuronal acetylcholine receptor / Neurotransmitter-gated ion-channel ...5-hydroxytryptamine 3 receptor / 5-hydroxytryptamine 3 receptor, A subunit / : / Neurotransmitter-gated ion-channel, conserved site / Neurotransmitter-gated ion-channels signature. / Neurotransmitter-gated ion-channel transmembrane domain / Neurotransmitter-gated ion-channel transmembrane region / Neurotransmitter-gated ion-channel transmembrane domain superfamily / Neuronal acetylcholine receptor / Neurotransmitter-gated ion-channel / Neurotransmitter-gated ion-channel ligand-binding domain / Neurotransmitter-gated ion-channel ligand-binding domain superfamily / Neurotransmitter-gated ion-channel ligand binding domain
Similarity search - Domain/homology
5-hydroxytryptamine receptor 3A
Similarity search - Component
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.3 Å
AuthorsLopez-Sanchez U / Nury H
Funding supportEuropean Union, 1 items
OrganizationGrant numberCountry
European Research Council (ERC)637733European Union
CitationJournal: 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 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
DepositionNov 9, 2022-
Header (metadata) releaseMay 15, 2024-
Map releaseMay 15, 2024-
UpdateJul 9, 2025-
Current statusJul 9, 2025Processing site: PDBe / Status: Released

-
Structure visualization

Supplemental images

emd_16105.png

Downloads & links

-
Map

FileDownload / File: emd_16105.map.gz / Format: CCP4 / Size: 64 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
1.14 Å/pix.
x 256 pix.
= 291.84 Å		1.14 Å/pix.
x 256 pix.
= 291.84 Å		1.14 Å/pix.
x 256 pix.
= 291.84 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 1.14 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.59
Minimum - Maximum-2.3812003 - 3.0673113
Average (Standard dev.)-0.0005309715 (±0.07299362)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions256256256
Spacing256256256
CellA=B=C: 291.84 Å
α=β=γ: 90.0 °

-
Supplemental data

-
Half map: #1

Fileemd_16105_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: #2

Fileemd_16105_half_map_2.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Sample components

-
Entire : Human 5HT3A receptor in complex with vortioxetine

EntireName: Human 5HT3A receptor in complex with vortioxetine
Components
  • Complex: Human 5HT3A receptor in complex with vortioxetine
    • Protein or peptide: 5-hydroxytryptamine receptor 3A
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose
  • Ligand: Vortioxetine

-
Supramolecule #1: Human 5HT3A receptor in complex with vortioxetine

SupramoleculeName: Human 5HT3A receptor in complex with vortioxetine / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1
Details: (nanodiscs, ECD only, active/distorted conformation)
Source (natural)Organism: Homo sapiens (human)

-
Macromolecule #1: 5-hydroxytryptamine receptor 3A

MacromoleculeName: 5-hydroxytryptamine receptor 3A / type: protein_or_peptide / ID: 1 / Number of copies: 5 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 52.172324 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: 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 LCLREQSTSQ RPPATSQATK TDDCSAMGNH CSHMGGPQDF EKSPRDRCSP PPPPREASLA VCGLLQELSS IRQF LEKRD EIREVARDWL RVGSVLDKLL FHIYLLAVLA YSITLVMLWS IWQYA

UniProtKB: 5-hydroxytryptamine receptor 3A

-
Macromolecule #3: 2-acetamido-2-deoxy-beta-D-glucopyranose

MacromoleculeName: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 3 / Number of copies: 5 / Formula: NAG
Molecular weightTheoretical: 221.208 Da
Chemical component information

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

-
Macromolecule #4: Vortioxetine

MacromoleculeName: Vortioxetine / type: ligand / ID: 4 / Number of copies: 5 / Formula: VTX
Molecular weightTheoretical: 298.446 Da

-
Experimental details

-
Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

-
Sample preparation

Concentration6.0 mg/mL
BufferpH: 7.4
VitrificationCryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 279 K / Instrument: FEI VITROBOT MARK IV

-
Electron microscopy

MicroscopeTFS GLACIOS
Image recordingFilm or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: COUNTING / Average electron dose: 40.0 e/Å2
Electron beamAcceleration voltage: 200 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.3000000000000003 µm / Nominal defocus min: 0.7000000000000001 µm

+
Image processing

CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
Startup modelType of model: OTHER
Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.3 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 31911
Initial angle assignmentType: OTHER
Final angle assignmentType: OTHER

+
About Yorodumi

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

New format data for meta-information of EMDB entries

  • Version 3 of the EMDB header file is now the official format.
  • The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

+
Mar 5, 2020. Novel coronavirus structure data

Novel coronavirus structure data

Related info.:Yorodumi Speices / Aug 12, 2020. Covid-19 info

External links:COVID-19 featured content - PDBj / Molecule of the Month (242)：Coronavirus Proteases

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

EMDB accession codes are about to change! (news from PDBe EMDB page)

  • The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator

External links:EMDB Accession Codes are Changing Soon! / Contact to PDBj

+
Jul 12, 2017. Major update of PDB

Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary.
  • This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software).
  • Now, EM Navigator and Yorodumi are based on the updated data.

External links:wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

-
Yorodumi

Thousand views of thousand structures

  • Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
  • This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
  • The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.

Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi

Read more