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- EMDB-65400: Cryo-EM structure of human noradrenaline transporter in complex w... -

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Basic information

Entry
Database: EMDB / ID: EMD-65400
TitleCryo-EM structure of human noradrenaline transporter in complex with tesofensine
Map data
Sample
  • Complex: Cryo-EM structure of human noradrenaline transporter in complex with tesofensine
    • Protein or peptide: Sodium-dependent noradrenaline transporter
  • Ligand: CHLORIDE ION
  • Ligand: (1~{R},2~{R},3~{S},5~{S})-3-(3,4-dichlorophenyl)-2-(ethoxymethyl)-8-methyl-8-azabicyclo[3.2.1]octane
KeywordsCryo-EM structure of human noradrenaline transporter in complex with tesofensine / MEMBRANE PROTEIN
Function / homology
Function and homology information


neurotransmitter:sodium symporter activity / Defective SLC6A2 causes orthostatic intolerance (OI) / norepinephrine uptake / : / norepinephrine:sodium symporter activity / dopamine:sodium symporter activity / neurotransmitter transmembrane transporter activity / monoamine transmembrane transporter activity / : / SLC-mediated transport of neurotransmitters ...neurotransmitter:sodium symporter activity / Defective SLC6A2 causes orthostatic intolerance (OI) / norepinephrine uptake / : / norepinephrine:sodium symporter activity / dopamine:sodium symporter activity / neurotransmitter transmembrane transporter activity / monoamine transmembrane transporter activity / : / SLC-mediated transport of neurotransmitters / dopamine uptake involved in synaptic transmission / neuronal cell body membrane / neurotransmitter transport / amino acid transport / alpha-tubulin binding / beta-tubulin binding / neuron cellular homeostasis / sodium ion transmembrane transport / synaptic vesicle membrane / actin binding / presynaptic membrane / chemical synaptic transmission / response to xenobiotic stimulus / axon / cell surface / membrane / metal ion binding / plasma membrane
Similarity search - Function
Sodium:neurotransmitter symporter, noradrenaline / 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 noradrenaline transporter
Similarity search - Component
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 2.9 Å
AuthorsZhao Y / Li Y / Meng Y
Funding support China, 1 items
OrganizationGrant numberCountry
Chinese Academy of Sciences China
CitationJournal: To Be Published
Title: Cryo-EM structure of human noradrenaline transporter in complex with tesofensine
Authors: Zhao Y / Li Y / Meng Y
History
DepositionJul 17, 2025-
Header (metadata) releaseJul 22, 2026-
Map releaseJul 22, 2026-
UpdateJul 22, 2026-
Current statusJul 22, 2026Processing site: PDBc / Status: Released

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Structure visualization

Supplemental images

emd_65400.png

Downloads & links

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Map

FileDownload / File: emd_65400.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: 0.2
Minimum - Maximum-1.7545235 - 2.4286225
Average (Standard dev.)0.00007827082 (±0.06689231)
SymmetrySpace group: 1
Details

EMDB XML:

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

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Supplemental data

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Half map: #2

Fileemd_65400_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Half map: #1

Fileemd_65400_half_map_2.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Sample components

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Entire : Cryo-EM structure of human noradrenaline transporter in complex w...

EntireName: Cryo-EM structure of human noradrenaline transporter in complex with tesofensine
Components
  • Complex: Cryo-EM structure of human noradrenaline transporter in complex with tesofensine
    • Protein or peptide: Sodium-dependent noradrenaline transporter
  • Ligand: CHLORIDE ION
  • Ligand: (1~{R},2~{R},3~{S},5~{S})-3-(3,4-dichlorophenyl)-2-(ethoxymethyl)-8-methyl-8-azabicyclo[3.2.1]octane

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Supramolecule #1: Cryo-EM structure of human noradrenaline transporter in complex w...

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

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Macromolecule #1: Sodium-dependent noradrenaline transporter

MacromoleculeName: Sodium-dependent noradrenaline transporter / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 63.801109 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: DAQPRETWGK KIDFLLSVVG FAVDLANVWR FPYLCYKNGG GAFLIPYTLF LIIAGMPLFY MELALGQYNR EGAATVWKIC PFFKGVGYA VILIALYVGF YYNVIIAWSL YYLFSSFTLN LPWTDCGHTW NSPNCTDPKL LNGSVLGNHT KYSKYKFTPA A EFYERGVL ...String:
DAQPRETWGK KIDFLLSVVG FAVDLANVWR FPYLCYKNGG GAFLIPYTLF LIIAGMPLFY MELALGQYNR EGAATVWKIC PFFKGVGYA VILIALYVGF YYNVIIAWSL YYLFSSFTLN LPWTDCGHTW NSPNCTDPKL LNGSVLGNHT KYSKYKFTPA A EFYERGVL HLHESSGIHD IGLPQWQLLL CLMVVVIVLY FSLWKGVKTS GKVVWITATL PYFVLFVLLV HGVTLPGASN GI NAYLHID FYRLKEATVW IDAATQIFFS LGAGFGVLIA FASYNKFDNN CYRDALLTSS INCITSFVSG FAIFSILGYM AHE HKVNIE DVATEGAGLV FILYPEAIST LSGSTFWAVV FFVMLLALGL DSSMGGMEAV ITGLADDFQV LKRHRKLFTF GVTF STFLL ALFCITKGGI YVLTLLDTFA AGTSILFAVL MEAIGVSWFY GVDRFSNDIQ QMMGFRPGLY WRLCWKFVSP AFLLF VVVV SIINFKPLTY DDYIFPPWAN WVGWGIALSS MVLVPIYVIY KFLSTQGSLW ERLAYGITPE NEHHLVAQRD IRQFQL QHW LAI

UniProtKB: Sodium-dependent noradrenaline transporter

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Macromolecule #2: CHLORIDE ION

MacromoleculeName: CHLORIDE ION / type: ligand / ID: 2 / Number of copies: 1 / Formula: CL
Molecular weightTheoretical: 35.453 Da

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Macromolecule #3: (1~{R},2~{R},3~{S},5~{S})-3-(3,4-dichlorophenyl)-2-(ethoxymethyl)...

MacromoleculeName: (1~{R},2~{R},3~{S},5~{S})-3-(3,4-dichlorophenyl)-2-(ethoxymethyl)-8-methyl-8-azabicyclo[3.2.1]octane
type: ligand / ID: 3 / Number of copies: 1 / Formula: A1EA1
Molecular weightTheoretical: 328.277 Da

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Experimental details

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Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

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Sample preparation

BufferpH: 7.5
VitrificationCryogen name: ETHANE

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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

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Image processing

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

8z1l

Final reconstructionResolution.type: BY AUTHOR / Resolution: 2.9 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC / Number images used: 155962
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD

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