[English] 日本語
Yorodumi
- EMDB-61182: Cryo-EM structure of human dopamine transporter in complex with c... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-61182
TitleCryo-EM structure of human dopamine transporter in complex with centanafadine
Map data
Sample
  • Complex: Cryo-EM structure of human dopamine transporter in complex with dasotraline
    • Protein or peptide: Sodium-dependent dopamine transporter
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose
  • Ligand: (1~{R},5~{S})-1-naphthalen-2-yl-3-azabicyclo[3.1.0]hexane
KeywordsCryo-EM structure of human dopamine transporter in complex with centanafadine / MEMBRANE PROTEIN
Function / homology
Function and homology information


Defective neurotransmitter clearance by SLC6A3 causes Parkinsonism-dystonia infantile (PKDYS) / Defective transport of neurotransmitters by SLC6A3 causes Parkinsonism-dystonia infantile (PKDYS) / Dopamine clearance from the synaptic cleft / amine binding / hyaloid vascular plexus regression / dopamine uptake / dopamine binding / norepinephrine:sodium symporter activity / dopamine:sodium symporter activity / response to leptin ...Defective neurotransmitter clearance by SLC6A3 causes Parkinsonism-dystonia infantile (PKDYS) / Defective transport of neurotransmitters by SLC6A3 causes Parkinsonism-dystonia infantile (PKDYS) / Dopamine clearance from the synaptic cleft / amine binding / hyaloid vascular plexus regression / dopamine uptake / dopamine binding / norepinephrine:sodium symporter activity / dopamine:sodium symporter activity / response to leptin / neurotransmitter transmembrane transporter activity / flotillin complex / monoamine transmembrane transporter activity / dopaminergic synapse / SLC-mediated transport of neurotransmitters / response to iron ion / heterocyclic compound binding / dopamine uptake involved in synaptic transmission / neurotransmitter transport / amino acid transport / response to cAMP / protein phosphatase 2A binding / axon terminus / response to nicotine / sodium ion transmembrane transport / protease binding / presynaptic membrane / response to ethanol / neuron projection / postsynaptic membrane / response to xenobiotic stimulus / membrane raft / signaling receptor binding / axon / neuronal cell body / protein-containing complex binding / cell surface / membrane / plasma membrane / cytoplasm
Similarity search - Function
Sodium:neurotransmitter symporter, dopamine / Sodium:neurotransmitter symporter family signature 2. / Sodium:neurotransmitter symporter family signature 1. / Sodium:neurotransmitter symporter / Sodium:neurotransmitter symporter superfamily / Sodium:neurotransmitter symporter family / Sodium:neurotransmitter symporter family profile.
Similarity search - Domain/homology
Sodium-dependent dopamine transporter
Similarity search - Component
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.4 Å
AuthorsZhao Y / Li Y
Funding support China, 1 items
OrganizationGrant numberCountry
Chinese Academy of Sciences China
CitationJournal: Nat Commun / Year: 2025
Title: Structural basis for pharmacotherapeutic action of triple reuptake inhibitors.
Authors: Yue Li / Yufei Meng / Na Li / Jun Zhao / Renjie Li / Qinru Bai / Gang Wang / Yan Zhao /
Abstract: Most first-line pharmacotherapeutic strategies for depression aim to boost serotonin and norepinephrine levels. However, 35% of patients with depression do not respond adequately to these treatments ...Most first-line pharmacotherapeutic strategies for depression aim to boost serotonin and norepinephrine levels. However, 35% of patients with depression do not respond adequately to these treatments or experience adverse side effects. The serotonin-norepinephrine-dopamine reuptake inhibitors, also known as triple reuptake inhibitors (TRIs), are emerging as promising antidepressants with greater potency and fewer side effects. Here, we determine an ensemble of structures of DAT in complex with five distinct TRIs. Tesofensine and dasotraline stabilize DAT in an outward-facing conformation, while centanafadine, ansofaxine, and nefazodone capture the inward-facing conformation. These structures reveal binding poses and interactions involved in the association of inhibitors. Notably, ansofaxine binds at a location which is much closer to the intracellular membrane surface. Through extensive structural analysis, we establish a comprehensive blueprint for the association of these TRIs, which is crucial for future drug development aimed at achieving potent antidepressant with fewer side effect.
History
DepositionAug 17, 2024-
Header (metadata) releaseMar 4, 2026-
Map releaseMar 4, 2026-
UpdateSep 16, 2026-
Current statusSep 16, 2026Processing site: PDBc / Status: Released

-
Structure visualization

Supplemental images

emd_61182.png

Downloads & links

-
Map

FileDownload / File: emd_61182.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.)
0.85 Å/pix.
x 256 pix.
= 217.6 Å		0.85 Å/pix.
x 256 pix.
= 217.6 Å		0.85 Å/pix.
x 256 pix.
= 217.6 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.85 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.22
Minimum - Maximum-1.2470002 - 1.4972852
Average (Standard dev.)0.0012562083 (±0.038299255)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions256256256
Spacing256256256
CellA=B=C: 217.6 Å
α=β=γ: 90.0 °

-
Supplemental data

-
Half map: #2

Fileemd_61182_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: #1

Fileemd_61182_half_map_2.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Sample components

-
Entire : Cryo-EM structure of human dopamine transporter in complex with d...

EntireName: Cryo-EM structure of human dopamine transporter in complex with dasotraline
Components
  • Complex: Cryo-EM structure of human dopamine transporter in complex with dasotraline
    • Protein or peptide: Sodium-dependent dopamine transporter
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose
  • Ligand: (1~{R},5~{S})-1-naphthalen-2-yl-3-azabicyclo[3.1.0]hexane

-
Supramolecule #1: Cryo-EM structure of human dopamine transporter in complex with d...

SupramoleculeName: Cryo-EM structure of human dopamine transporter in complex with dasotraline
type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1
Source (natural)Organism: Homo sapiens (human)

-
Macromolecule #1: Sodium-dependent dopamine transporter

MacromoleculeName: Sodium-dependent dopamine transporter / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 61.590508 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: KIDFLLSVIG FAVDLANVWR FPYLCYKNGG GAFLVPYLLF MVIAGMPLFY MELALGQFNR EGAAGVWKIC PILKGVGFTV ILISLYVGF FYNVIIAWAL HYLFSSFTTE LPWIHCNNSW NSPNCSDAHP GDSSGDSSGL NDTFGTTPAA EYFERGVLHL H QSHGIDDL ...String:
KIDFLLSVIG FAVDLANVWR FPYLCYKNGG GAFLVPYLLF MVIAGMPLFY MELALGQFNR EGAAGVWKIC PILKGVGFTV ILISLYVGF FYNVIIAWAL HYLFSSFTTE LPWIHCNNSW NSPNCSDAHP GDSSGDSSGL NDTFGTTPAA EYFERGVLHL H QSHGIDDL GPPRWQLTAC LVLVIVLLYF SLWKGVKTSG KVVWITATMP YVVLTALLLR GVTLPGAIDG IRAYLSVDFY RL CEASVWI DAATQVCFSL GVGFGVLIAF SSYNKFTNNC YRDAIVTTSI NSLTSFSSGF VVFSFLGYMA QKHSVPIGDV AKD GPGLIF IIYPEAIATL PLSSAWAVVF FIMLLTLGID SAMGGMESVI TGLIDEFQLL HRHRELFTLF IVLATFLLSL FCVT NGGIY VFTLLDHFAA GTSILFGVLI EAIGVAWFYG VGQFSDDIQQ MTGQRPSLYW RLCWKLVSPC FLLFVVVVSI VTFRP PHYG AYIFPDWANA LGWVIATSSM AMVPIYAAYK FCSLPGSFRE KLAYAIAPEK DRELVDRGEV RQFTLRHWLK V

UniProtKB: Sodium-dependent dopamine transporter

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

MacromoleculeName: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 2 / Number of copies: 1 / Formula: NAG
Molecular weightTheoretical: 221.208 Da
Chemical component information

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

-
Macromolecule #3: (1~{R},5~{S})-1-naphthalen-2-yl-3-azabicyclo[3.1.0]hexane

MacromoleculeName: (1~{R},5~{S})-1-naphthalen-2-yl-3-azabicyclo[3.1.0]hexane
type: ligand / ID: 3 / Number of copies: 1 / Formula: A1EA2
Molecular weightTheoretical: 209.286 Da

-
Experimental details

-
Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

-
Sample preparation

BufferpH: 7.5
VitrificationCryogen name: ETHANE

-
Electron microscopy

MicroscopeTFS KRIOS
Image recordingFilm or detector model: GATAN K3 (6k x 4k) / Average electron dose: 60.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.0 µm / Nominal defocus min: 1.0 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

+
Image processing

CTF correctionType: PHASE FLIPPING ONLY
Startup modelType of model: PDB ENTRY
PDB model - PDB ID:

8y2c

Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.4 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC (ver. v4.7.0) / Number images used: 52169
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD

+
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