[English] 日本語
![](img/lk-miru.gif)
- PDB-8wgx: Cryo-EM structure of inward-open state human norepinephrine trans... -
+
Open data
-
Basic information
Entry | Database: PDB / ID: 8wgx | ||||||
---|---|---|---|---|---|---|---|
Title | Cryo-EM structure of inward-open state human norepinephrine transporter NET bound with norepinephrine in nanodisc. | ||||||
![]() | Sodium-dependent noradrenaline transporter | ||||||
![]() | MEMBRANE PROTEIN / Norepinephrine transporter / NET / SLC6A2 / norepinephrine / dopamine / neurotransmitter / desipramine / bupropion / antidepressant. / TRANSPORT PROTEIN | ||||||
Function / homology | ![]() 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 | ![]() | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.47 Å | ||||||
![]() | Tan, J. / Xiao, Y. / Kong, F. / Lei, J. / Yuan, Y. / Yan, C. | ||||||
Funding support | ![]()
| ||||||
![]() | ![]() Title: Molecular basis of human noradrenaline transporter reuptake and inhibition. Authors: Jiaxin Tan / Yuan Xiao / Fang Kong / Xiaochun Zhang / Hanwen Xu / Angqi Zhu / Yiming Liu / Jianlin Lei / Boxue Tian / Yafei Yuan / Chuangye Yan / ![]() Abstract: Noradrenaline, also known as norepinephrine, has a wide range of activities and effects on most brain cell types. Its reuptake from the synaptic cleft heavily relies on the noradrenaline transporter ...Noradrenaline, also known as norepinephrine, has a wide range of activities and effects on most brain cell types. Its reuptake from the synaptic cleft heavily relies on the noradrenaline transporter (NET) located in the presynaptic membrane. Here we report the cryo-electron microscopy (cryo-EM) structures of the human NET in both its apo state and when bound to substrates or antidepressant drugs, with resolutions ranging from 2.5 Å to 3.5 Å. The two substrates, noradrenaline and dopamine, display a similar binding mode within the central substrate binding site (S1) and within a newly identified extracellular allosteric site (S2). Four distinct antidepressants, namely, atomoxetine, desipramine, bupropion and escitalopram, occupy the S1 site to obstruct substrate transport in distinct conformations. Moreover, a potassium ion was observed within sodium-binding site 1 in the structure of the NET bound to desipramine under the KCl condition. Complemented by structural-guided biochemical analyses, our studies reveal the mechanism of substrate recognition, the alternating access of NET, and elucidate the mode of action of the four antidepressants. | ||||||
History |
|
-
Structure visualization
Structure viewer | Molecule: ![]() ![]() |
---|
-
Downloads & links
-
Download
PDBx/mmCIF format | ![]() | 191.6 KB | Display | ![]() |
---|---|---|---|---|
PDB format | ![]() | 152.7 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
---|
-Related structure data
Related structure data | ![]() 37520MC ![]() 8hfeC ![]() 8hffC ![]() 8hfgC ![]() 8hfiC ![]() 8hflC ![]() 8i3vC ![]() 8wgrC ![]() 8z1lC C: citing same article ( M: map data used to model this data |
---|---|
Similar structure data | Similarity search - Function & homology ![]() |
-
Links
-
Assembly
Deposited unit | ![]()
|
---|---|
1 |
|
-
Components
#1: Protein | Mass: 69386.547 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() | ||
---|---|---|---|
#2: Chemical | Has ligand of interest | Y | |
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
---|---|
EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-
Sample preparation
Component | Name: NET / Type: COMPLEX / Entity ID: #1 / Source: RECOMBINANT |
---|---|
Molecular weight | Value: 0.11 MDa / Experimental value: NO |
Source (natural) | Organism: ![]() |
Source (recombinant) | Organism: ![]() |
Buffer solution | pH: 8 |
Specimen | Conc.: 10 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
-
Electron microscopy imaging
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
---|---|
Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: ![]() |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 1400 nm / Nominal defocus min: 1000 nm |
Image recording | Electron dose: 50 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
-
Processing
EM software |
| ||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
CTF correction | Type: NONE | ||||||||||||||||||||||||
Symmetry | Point symmetry: C1 (asymmetric) | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.47 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 150374 / Symmetry type: POINT | ||||||||||||||||||||||||
Refine LS restraints |
|