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- EMDB-37520: Cryo-EM structure of inward-open state human norepinephrine trans... -

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Basic information

Entry
Database: EMDB / ID: EMD-37520
TitleCryo-EM structure of inward-open state human norepinephrine transporter NET bound with norepinephrine in nanodisc.
Map data
Sample
  • Complex: NET
    • Protein or peptide: Sodium-dependent noradrenaline transporter
  • Ligand: L-NOREPINEPHRINE
KeywordsNorepinephrine transporter / NET / SLC6A2 / norepinephrine / dopamine / neurotransmitter / desipramine / bupropion / antidepressant. / TRANSPORT PROTEIN / MEMBRANE PROTEIN
Function / homology
Function and homology information


neurotransmitter:sodium symporter activity / Defective SLC6A2 causes orthostatic intolerance (OI) / norepinephrine uptake / dopamine:sodium symporter activity / norepinephrine:sodium symporter activity / norepinephrine transport / neurotransmitter transmembrane transporter activity / monoamine transmembrane transporter activity / Na+/Cl- dependent neurotransmitter transporters / monoamine transport ...neurotransmitter:sodium symporter activity / Defective SLC6A2 causes orthostatic intolerance (OI) / norepinephrine uptake / dopamine:sodium symporter activity / norepinephrine:sodium symporter activity / norepinephrine transport / neurotransmitter transmembrane transporter activity / monoamine transmembrane transporter activity / Na+/Cl- dependent neurotransmitter transporters / monoamine transport / neurotransmitter transport / dopamine uptake involved in synaptic transmission / amino acid transport / response to pain / neuronal cell body membrane / beta-tubulin binding / alpha-tubulin binding / sodium ion transmembrane transport / neuron cellular homeostasis / presynaptic membrane / actin binding / 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: 3.47 Å
AuthorsTan J / Xiao Y / Kong F / Lei J / Yuan Y / Yan C
Funding support China, 1 items
OrganizationGrant numberCountry
Ministry of Science and Technology (MoST, China)2020YFA0509301 China
CitationJournal: Nature / Year: 2024
Title: Molecular basis of human noradrenaline transporter reuptake and inhibition.
Authors: Tan J / Xiao Y / Kong F / Zhang X / Xu H / Zhu A / Liu Y / Lei J / Tian J / Yuan Y / Yan C
History
DepositionSep 22, 2023-
Header (metadata) releaseJul 31, 2024-
Map releaseJul 31, 2024-
UpdateJul 31, 2024-
Current statusJul 31, 2024Processing site: PDBj / Status: Released

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Structure visualization

Supplemental images

emd_37520.png

Downloads & links

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Map

FileDownload / File: emd_37520.map.gz / Format: CCP4 / Size: 27 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
1.08 Å/pix.
x 192 pix.
= 207.84 Å		1.08 Å/pix.
x 192 pix.
= 207.84 Å		1.08 Å/pix.
x 192 pix.
= 207.84 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 1.0825 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.7
Minimum - Maximum-3.195097 - 4.5085354
Average (Standard dev.)0.0055417554 (±0.10651861)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions192192192
Spacing192192192
CellA=B=C: 207.84 Å
α=β=γ: 90.0 °

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Supplemental data

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Mask #1

Fileemd_37520_msk_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Half map: #2

Fileemd_37520_half_map_1.map
Projections & Slices
AxesZYX

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Density Histograms

Histogram

Histogram (log scale)

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Half map: #1

Fileemd_37520_half_map_2.map
Projections & Slices
AxesZYX

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Slices (1/2)
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Histogram

Histogram (log scale)

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Sample components

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Entire : NET

EntireName: NET
Components
  • Complex: NET
    • Protein or peptide: Sodium-dependent noradrenaline transporter
  • Ligand: L-NOREPINEPHRINE

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Supramolecule #1: NET

SupramoleculeName: NET / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 110 KDa

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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: 69.386547 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: MLLARMNPQV QPENNGADTG PEQPLRARKT AELLVVKERN GVQCLLAPRD GDAQPRETWG KKIDFLLSVV GFAVDLANVW RFPYLCYKN GGGAFLIPYT LFLIIAGMPL FYMELALGQY NREGAATVWK ICPFFKGVGY AVILIALYVG FYYNVIIAWS L YYLFSSFT ...String:
MLLARMNPQV QPENNGADTG PEQPLRARKT AELLVVKERN GVQCLLAPRD GDAQPRETWG KKIDFLLSVV GFAVDLANVW RFPYLCYKN GGGAFLIPYT LFLIIAGMPL FYMELALGQY NREGAATVWK ICPFFKGVGY AVILIALYVG FYYNVIIAWS L YYLFSSFT LNLPWTDCGH TWNSPNCTDP KLLNGSVLGN HTKYSKYKFT PAAEFYERGV LHLHESSGIH DIGLPQWQLL LC LMVVVIV LYFSLWKGVK TSGKVVWITA TLPYFVLFVL LVHGVTLPGA SNGINAYLHI DFYRLKEATV WIDAATQIFF SLG AGFGVL IAFASYNKFD NNCYRDALLT SSINCITSFV SGFAIFSILG YMAHEHKVNI EDVATEGAGL VFILYPEAIS TLSG STFWA VVFFVMLLAL GLDSSMGGME AVITGLADDF QVLKRHRKLF TFGVTFSTFL LALFCITKGG IYVLTLLDTF AAGTS ILFA VLMEAIGVSW FYGVDRFSND IQQMMGFRPG LYWRLCWKFV SPAFLLFVVV VSIINFKPLT YDDYIFPPWA NWVGWG IAL SSMVLVPIYV IYKFLSTQGS LWERLAYGIT PENEHHLVAQ RDIRQFQLQH WLAI

UniProtKB: Sodium-dependent noradrenaline transporter

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Macromolecule #2: L-NOREPINEPHRINE

MacromoleculeName: L-NOREPINEPHRINE / type: ligand / ID: 2 / Number of copies: 2 / Formula: LNR
Molecular weightTheoretical: 169.178 Da
Chemical component information

ChemComp-LNR:
L-NOREPINEPHRINE / neurotransmitter, hormone*YM

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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

Concentration10 mg/mL
BufferpH: 8
VitrificationCryogen name: ETHANE

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Electron microscopy

MicroscopeFEI TITAN KRIOS
Image recordingFilm or detector model: GATAN K3 (6k x 4k) / Average electron dose: 50.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 1.4000000000000001 µm / Nominal defocus min: 1.0 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

Startup modelType of model: NONE
Final reconstructionApplied symmetry - Point group: C1 (asymmetric) / Resolution.type: BY AUTHOR / Resolution: 3.47 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC / Number images used: 150374
Initial angle assignmentType: MAXIMUM LIKELIHOOD / Software - Name: cryoSPARC
Final angle assignmentType: MAXIMUM LIKELIHOOD / Software - Name: cryoSPARC

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