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- PDB-6xiw: Cryo-EM structure of the sodium leak channel NALCN-FAM155A complex -
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Open data
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Basic information
Entry | Database: PDB / ID: 6xiw | ||||||
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Title | Cryo-EM structure of the sodium leak channel NALCN-FAM155A complex | ||||||
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![]() | MEMBRANE PROTEIN / ion channel / complex / cysteine rich domain | ||||||
Function / homology | ![]() stretch-activated, monoatomic cation-selective, calcium channel activity / positive regulation of synaptic transmission, cholinergic / leak channel activity / regulation of resting membrane potential / sodium channel activity / monoatomic ion channel complex / voltage-gated sodium channel activity / sodium ion transmembrane transport / calcium ion import across plasma membrane / monoatomic cation channel activity ...stretch-activated, monoatomic cation-selective, calcium channel activity / positive regulation of synaptic transmission, cholinergic / leak channel activity / regulation of resting membrane potential / sodium channel activity / monoatomic ion channel complex / voltage-gated sodium channel activity / sodium ion transmembrane transport / calcium ion import across plasma membrane / monoatomic cation channel activity / monoatomic ion transmembrane transport / potassium ion transmembrane transport / positive regulation of synaptic transmission, GABAergic / calcium ion transmembrane transport / Stimuli-sensing channels / plasma membrane Similarity search - Function | ||||||
Biological species | ![]() | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.8 Å | ||||||
![]() | Kschonsak, M. / Chua, H.C. / Noland, C.L. / Weidling, C. / Clairfeuille, T. / Bahlke, O.O. / Ameen, A.O. / Li, Z.R. / Arthur, C.P. / Ciferri, C. ...Kschonsak, M. / Chua, H.C. / Noland, C.L. / Weidling, C. / Clairfeuille, T. / Bahlke, O.O. / Ameen, A.O. / Li, Z.R. / Arthur, C.P. / Ciferri, C. / Pless, S.A. / Payandeh, J. | ||||||
![]() | ![]() Title: Structure of the human sodium leak channel NALCN. Authors: Marc Kschonsak / Han Chow Chua / Cameron L Noland / Claudia Weidling / Thomas Clairfeuille / Oskar Ørts Bahlke / Aishat Oluwanifemi Ameen / Zhong Rong Li / Christopher P Arthur / Claudio ...Authors: Marc Kschonsak / Han Chow Chua / Cameron L Noland / Claudia Weidling / Thomas Clairfeuille / Oskar Ørts Bahlke / Aishat Oluwanifemi Ameen / Zhong Rong Li / Christopher P Arthur / Claudio Ciferri / Stephan Alexander Pless / Jian Payandeh / ![]() ![]() Abstract: Persistently depolarizing sodium (Na) leak currents enhance electrical excitability. The ion channel responsible for the major background Na conductance in neurons is the Na leak channel, non- ...Persistently depolarizing sodium (Na) leak currents enhance electrical excitability. The ion channel responsible for the major background Na conductance in neurons is the Na leak channel, non-selective (NALCN). NALCN-mediated currents regulate neuronal excitability linked to respiration, locomotion and circadian rhythm. NALCN activity is under tight regulation and mutations in NALCN cause severe neurological disorders and early death. NALCN is an orphan channel in humans, and fundamental aspects of channel assembly, gating, ion selectivity and pharmacology remain obscure. Here we investigate this essential leak channel and determined the structure of NALCN in complex with a distinct auxiliary subunit, family with sequence similarity 155 member A (FAM155A). FAM155A forms an extracellular dome that shields the ion-selectivity filter from neurotoxin attack. The pharmacology of NALCN is further delineated by a walled-off central cavity with occluded lateral pore fenestrations. Unusual voltage-sensor domains with asymmetric linkages to the pore suggest mechanisms by which NALCN activity is modulated. We found a tightly closed pore gate in NALCN where the majority of missense patient mutations cause gain-of-function phenotypes that cluster around the S6 gate and distinctive π-bulges. Our findings provide a framework to further study the physiology of NALCN and a foundation for discovery of treatments for NALCN channelopathies and other electrical disorders. | ||||||
History |
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Structure visualization
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Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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PDBx/mmCIF format | ![]() | 282.5 KB | Display | ![]() |
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PDB format | ![]() | 225.2 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 1.4 MB | Display | ![]() |
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Full document | ![]() | 1.4 MB | Display | |
Data in XML | ![]() | 45.1 KB | Display | |
Data in CIF | ![]() | 65.7 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 22203MC M: map data used to model this data C: citing same article ( |
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Similar structure data |
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Links
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Assembly
Deposited unit | ![]()
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Components
-Protein , 2 types, 2 molecules AB
#1: Protein | Mass: 206341.641 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Details: TYR287 modeled with sulfonation (TYS) as the EM density indicates a post-translational modification of this residue. Source: (gene. exp.) ![]() ![]() |
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#2: Protein | Mass: 54205.004 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
-Sugars , 1 types, 2 molecules ![](data/chem/img/NAG.gif)
#3: Sugar |
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-Non-polymers , 4 types, 15 molecules ![](data/chem/img/PEV.gif)
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![](data/chem/img/HOH.gif)
![](data/chem/img/PGV.gif)
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#4: Chemical | ChemComp-PEV / ( #5: Chemical | #6: Chemical | #7: Water | ChemComp-HOH / | |
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-Details
Has ligand of interest | N |
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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 |
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Sample preparation
Component | Name: NALCN in complex with FAM155A / Type: COMPLEX Details: NALCN, FAM155A, UNC80 and UNC79 co-expressed and NALCN-FAM155A co-purified Entity ID: #1-#2 / Source: RECOMBINANT | ||||||||||||||||||||
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Molecular weight | Experimental value: NO | ||||||||||||||||||||
Source (natural) | Organism: ![]() | ||||||||||||||||||||
Source (recombinant) | Organism: ![]() | ||||||||||||||||||||
Buffer solution | pH: 7.5 | ||||||||||||||||||||
Buffer component |
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Specimen | Conc.: 2.4 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES Details: sample was gently cross-linked with 0.05% EM-grade glutaraldehyde for 10 min at room temperature and quenched with 0.09 M TRIS pH 7.5 | ||||||||||||||||||||
Specimen support | Grid material: GOLD / Grid mesh size: 200 divisions/in. / Grid type: UltrAuFoil R2/2 | ||||||||||||||||||||
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 277 K |
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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: ![]() |
Electron lens | Mode: BRIGHT FIELD / Nominal magnification: 165000 X / Cs: 2.7 mm / C2 aperture diameter: 70 µm |
Specimen holder | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Image recording | Average exposure time: 10 sec. / Electron dose: 49.967 e/Å2 / Detector mode: COUNTING / Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Num. of grids imaged: 1 / Num. of real images: 15080 |
EM imaging optics | Energyfilter name: GIF Quantum LS / Energyfilter slit width: 20 eV |
Image scans | Movie frames/image: 50 |
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Processing
EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
Particle selection | Num. of particles selected: 1778009 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
Symmetry | Point symmetry: C1 (asymmetric) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 2.8 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 365512 / Symmetry type: POINT | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
Atomic model building | Space: REAL |