+Open data
-Basic information
Entry | Database: PDB / ID: 8y94 | ||||||
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Title | Structure of Apo human norepinephrine transporter NET | ||||||
Components | Sodium-dependent noradrenaline transporter | ||||||
Keywords | TRANSPORT PROTEIN / neurotransmitter / transporters | ||||||
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 / 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 / norepinephrine:sodium symporter activity / dopamine: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 / response to pain / amino acid transport / 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 | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.29 Å | ||||||
Authors | Zhang, H. / Xu, H.E. / Jiang, Y. | ||||||
Funding support | China, 1items
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Citation | Journal: Nature / Year: 2024 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
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8y94.cif.gz | 201.5 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8y94.ent.gz | 162.5 KB | Display | PDB format |
PDBx/mmJSON format | 8y94.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/y9/8y94 ftp://data.pdbj.org/pub/pdb/validation_reports/y9/8y94 | HTTPS FTP |
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-Related structure data
Related structure data | 39069MC 8y8zC 8y90C 8y91C 8y92C 8y93C 8y95C 8yr2C M: map data used to model this data C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
#1: Protein | Mass: 69386.547 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: NET1 / Production host: Homo sapiens (human) / References: UniProt: P23975 |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: structure of Apo human NET / Type: COMPLEX / Entity ID: all / Source: RECOMBINANT |
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Molecular weight | Value: 0.1 MDa / Experimental value: YES |
Source (natural) | Organism: Homo sapiens (human) |
Source (recombinant) | Organism: Homo sapiens (human) |
Buffer solution | pH: 7.5 |
Specimen | Conc.: 1.5 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 283 K |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: SPOT SCAN |
Electron lens | Mode: DIFFRACTION / Nominal defocus max: 2500 nm / Nominal defocus min: 1000 nm / Cs: 2.7 mm |
Image recording | Electron dose: 50 e/Å2 / Film or detector model: FEI FALCON IV (4k x 4k) |
-Processing
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
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3D reconstruction | Resolution: 3.29 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 92707 / Symmetry type: POINT |