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Open data
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Basic information
Entry | ![]() | |||||||||
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Title | Structure of NET-NE in Occluded state | |||||||||
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![]() | substrate / transporter / TRANSPORT PROTEIN | |||||||||
Function / homology | ![]() 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 / sodium ion transmembrane transport / alpha-tubulin binding / 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 | |||||||||
Biological species | ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.24 Å | |||||||||
![]() | Zhang H / Xu HE / Jiang Y | |||||||||
Funding support | ![]()
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![]() | ![]() Title: Dimerization and antidepressant recognition at noradrenaline transporter. Authors: Heng Zhang / Yu-Ling Yin / Antao Dai / Tianwei Zhang / Chao Zhang / Canrong Wu / Wen Hu / Xinheng He / Benxun Pan / Sanshan Jin / Qingning Yuan / Ming-Wei Wang / Dehua Yang / H Eric Xu / Yi Jiang / ![]() Abstract: The noradrenaline transporter has a pivotal role in regulating neurotransmitter balance and is crucial for normal physiology and neurobiology. Dysfunction of noradrenaline transporter has been ...The noradrenaline transporter has a pivotal role in regulating neurotransmitter balance and is crucial for normal physiology and neurobiology. Dysfunction of noradrenaline transporter has been implicated in numerous neuropsychiatric diseases, including depression and attention deficit hyperactivity disorder. Here we report cryo-electron microscopy structures of noradrenaline transporter in apo and substrate-bound forms, and as complexes with six antidepressants. The structures reveal a noradrenaline transporter dimer interface that is mediated predominantly by cholesterol and lipid molecules. The substrate noradrenaline binds deep in the central binding pocket, and its amine group interacts with a conserved aspartate residue. Our structures also provide insight into antidepressant recognition and monoamine transporter selectivity. Together, these findings advance our understanding of noradrenaline transporter regulation and inhibition, and provide templates for designing improved antidepressants to treat neuropsychiatric disorders. | |||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 117.8 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 14.8 KB 14.8 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 10.6 KB | Display | ![]() |
Images | ![]() | 98.7 KB | ||
Filedesc metadata | ![]() | 5.6 KB | ||
Others | ![]() ![]() | 115.7 MB 115.7 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 1 MB | Display | ![]() |
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Full document | ![]() | 1 MB | Display | |
Data in XML | ![]() | 18.9 KB | Display | |
Data in CIF | ![]() | 24.2 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8y95MC ![]() 8y8zC ![]() 8y90C ![]() 8y91C ![]() 8y92C ![]() 8y93C ![]() 8y94C ![]() 8yr2C M: atomic model generated by this map C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Voxel size | X=Y=Z: 0.73 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: #2
File | emd_39070_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_39070_half_map_2.map | ||||||||||||
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Density Histograms |
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Sample components
-Entire : Sodium-dependent noradrenaline transporter bound noradrenaline
Entire | Name: Sodium-dependent noradrenaline transporter bound noradrenaline |
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Components |
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-Supramolecule #1: Sodium-dependent noradrenaline transporter bound noradrenaline
Supramolecule | Name: Sodium-dependent noradrenaline transporter bound noradrenaline type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1 |
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Source (natural) | Organism: ![]() |
-Macromolecule #1: Sodium-dependent noradrenaline transporter
Macromolecule | Name: Sodium-dependent noradrenaline transporter / type: protein_or_peptide / ID: 1 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 69.386547 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: 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 |
-Macromolecule #2: Noradrenaline
Macromolecule | Name: Noradrenaline / type: ligand / ID: 2 / Number of copies: 2 / Formula: E5E |
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Molecular weight | Theoretical: 170.186 Da |
Chemical component information | ![]() ChemComp-E5E: |
-Macromolecule #3: CHLORIDE ION
Macromolecule | Name: CHLORIDE ION / type: ligand / ID: 3 / Number of copies: 2 / Formula: CL |
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Molecular weight | Theoretical: 35.453 Da |
-Macromolecule #4: SODIUM ION
Macromolecule | Name: SODIUM ION / type: ligand / ID: 4 / Number of copies: 2 |
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Molecular weight | Theoretical: 22.99 Da |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Buffer | pH: 7.5 |
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Vitrification | Cryogen name: ETHANE |
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Electron microscopy
Microscope | FEI TITAN |
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Image recording | Film or detector model: FEI FALCON IV (4k x 4k) / Average electron dose: 50.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: SPOT SCAN / Imaging mode: DIFFRACTION / Nominal defocus max: 2.0 µm / Nominal defocus min: 1.0 µm |