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- EMDB-62276: Cryo-EM structure of LIPID-mediated dimer of human norepinephrine... -

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Basic information

Entry
Database: EMDB / ID: EMD-62276
TitleCryo-EM structure of LIPID-mediated dimer of human norepinephrine transporter NET in the presence of Vanoxerine in an inward-open state at resolution of 2.52 angstrom
Map data
Sample
  • Complex: Sodium-dependent noradrenaline transporter
    • Protein or peptide: Sodium-dependent noradrenaline transporter
  • Ligand: CHOLESTEROL
  • Ligand: Vanoxerine
  • Ligand: [(2~{R})-1-[[(2~{S})-2,3-bis(oxidanyl)propoxy]-oxidanyl-phosphoryl]oxy-3-nonanoyloxy-propan-2-yl] decanoate
KeywordsCOMPLEX / TRANSPORT PROTEIN
Function / homology
Function and homology information


neurotransmitter:sodium symporter activity / Defective SLC6A2 causes orthostatic intolerance (OI) / norepinephrine uptake / norepinephrine:sodium symporter activity / norepinephrine transport / dopamine:sodium symporter activity / neurotransmitter transmembrane transporter activity / monoamine transmembrane transporter activity / monoamine transport / SLC-mediated transport of neurotransmitters ...neurotransmitter:sodium symporter activity / Defective SLC6A2 causes orthostatic intolerance (OI) / norepinephrine uptake / norepinephrine:sodium symporter activity / norepinephrine transport / dopamine:sodium symporter activity / neurotransmitter transmembrane transporter activity / monoamine transmembrane transporter activity / monoamine transport / SLC-mediated transport of neurotransmitters / neuronal cell body membrane / response to pain / neurotransmitter transport / amino acid transport / dopamine uptake involved in synaptic transmission / alpha-tubulin binding / beta-tubulin binding / sodium ion transmembrane transport / neuron cellular homeostasis / synaptic vesicle membrane / presynaptic membrane / actin binding / chemical synaptic transmission / response to xenobiotic stimulus / axon / cell surface / metal ion binding / membrane / 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: 2.52 Å
AuthorsZhang H / Xu EH / Jiang Y
Funding support China, 1 items
OrganizationGrant numberCountry
National Natural Science Foundation of China (NSFC) China
CitationJournal: To Be Published
Title: Cryo-EM structure of LIPID-mediated dimer of human norepinephrine transporter NET in the presence of Vanoxerine in an inward-open state at resolution of 2.52 angstrom
Authors: Zhang H / Xu EH / Jiang Y
History
DepositionNov 3, 2024-
Header (metadata) releaseNov 19, 2025-
Map releaseNov 19, 2025-
UpdateNov 19, 2025-
Current statusNov 19, 2025Processing site: PDBc / Status: Released

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Structure visualization

Supplemental images

emd_62276.png

Downloads & links

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Map

FileDownload / File: emd_62276.map.gz / Format: CCP4 / Size: 125 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.73 Å/pix.
x 320 pix.
= 233.6 Å		0.73 Å/pix.
x 320 pix.
= 233.6 Å		0.73 Å/pix.
x 320 pix.
= 233.6 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.73 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.2
Minimum - Maximum-2.0774338 - 3.0059032
Average (Standard dev.)0.00074813765 (±0.08184056)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions320320320
Spacing320320320
CellA=B=C: 233.6 Å
α=β=γ: 90.0 °

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Supplemental data

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Half map: #2

Fileemd_62276_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_62276_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 : Sodium-dependent noradrenaline transporter

EntireName: Sodium-dependent noradrenaline transporter
Components
  • Complex: Sodium-dependent noradrenaline transporter
    • Protein or peptide: Sodium-dependent noradrenaline transporter
  • Ligand: CHOLESTEROL
  • Ligand: Vanoxerine
  • Ligand: [(2~{R})-1-[[(2~{S})-2,3-bis(oxidanyl)propoxy]-oxidanyl-phosphoryl]oxy-3-nonanoyloxy-propan-2-yl] decanoate

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Supramolecule #1: Sodium-dependent noradrenaline transporter

SupramoleculeName: Sodium-dependent noradrenaline transporter / 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: 2 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 70.715875 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: MDYKDDDDKG SGMLLARMNP QVQPENNGAD TGPEQPLRAR KTAELLVVKE RNGVQCLLAP RDGDAQPRET WGKKIDFLLS VVGFAVDLA NVWRFPYLCY KNGGGAFLIP YTLFLIIAGM PLFYMELALG QYNREGAATV WKICPFFKGV GYAVILIALY V GFYYNVII ...String:
MDYKDDDDKG SGMLLARMNP QVQPENNGAD TGPEQPLRAR KTAELLVVKE RNGVQCLLAP RDGDAQPRET WGKKIDFLLS VVGFAVDLA NVWRFPYLCY KNGGGAFLIP YTLFLIIAGM PLFYMELALG QYNREGAATV WKICPFFKGV GYAVILIALY V GFYYNVII AWSLYYLFSS FTLNLPWTDC GHTWNSPNCT DPKLLNGSVL GNHTKYSKYK FTPAAEFYER GVLHLHESSG IH DIGLPQW QLLLCLMVVV IVLYFSLWKG VKTSGKVVWI TATLPYFVLF VLLVHGVTLP GASNGINAYL HIDFYRLKEA TVW IDAATQ IFFSLGAGFG VLIAFASYNK FDNNCYRDAL LTSSINCITS FVSGFAIFSI LGYMAHEHKV NIEDVATEGA GLVF ILYPE AISTLSGSTF WAVVFFVMLL ALGLDSSMGG MEAVITGLAD DFQVLKRHRK LFTFGVTFST FLLALFCITK GGIYV LTLL DTFAAGTSIL FAVLMEAIGV SWFYGVDRFS NDIQQMMGFR PGLYWRLCWK FVSPAFLLFV VVVSIINFKP LTYDDY IFP PWANWVGWGI ALSSMVLVPI YVIYKFLSTQ GSLWERLAYG ITPENEHHLV AQRDIRQFQL QHWLAI

UniProtKB: Sodium-dependent noradrenaline transporter

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Macromolecule #2: CHOLESTEROL

MacromoleculeName: CHOLESTEROL / type: ligand / ID: 2 / Number of copies: 14 / Formula: CLR
Molecular weightTheoretical: 386.654 Da
Chemical component information

ChemComp-CLR:
CHOLESTEROL

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Macromolecule #3: Vanoxerine

MacromoleculeName: Vanoxerine / type: ligand / ID: 3 / Number of copies: 2 / Formula: A1D5S
Molecular weightTheoretical: 450.563 Da

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Macromolecule #4: [(2~{R})-1-[[(2~{S})-2,3-bis(oxidanyl)propoxy]-oxidanyl-phosphory...

MacromoleculeName: [(2~{R})-1-[[(2~{S})-2,3-bis(oxidanyl)propoxy]-oxidanyl-phosphoryl]oxy-3-nonanoyloxy-propan-2-yl] decanoate
type: ligand / ID: 4 / Number of copies: 2 / Formula: A1EFM
Molecular weightTheoretical: 540.624 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: FEI FALCON IV (4k x 4k) / Average electron dose: 50.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: SPOT SCAN / Imaging mode: DIFFRACTION / Nominal defocus max: 3.0 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 AND AMPLITUDE CORRECTION
Startup modelType of model: NONE
Final reconstructionResolution.type: BY AUTHOR / Resolution: 2.52 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC / Number images used: 200579
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD
FSC plot (resolution estimation)

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