+Open data
-Basic information
Entry | Database: PDB / ID: 6uz3 | |||||||||
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Title | Cardiac sodium channel | |||||||||
Components | Sodium channel protein type 5 subunit alpha,Green fluorescent protein | |||||||||
Keywords | METAL TRANSPORT / cardiac sodium channel / ion channel | |||||||||
Function / homology | Function and homology information voltage-gated sodium channel activity involved in AV node cell action potential / voltage-gated sodium channel activity involved in bundle of His cell action potential / voltage-gated sodium channel activity involved in SA node cell action potential / bundle of His cell action potential / AV node cell action potential / sodium channel complex / SA node cell action potential / AV node cell to bundle of His cell communication / membrane depolarization during SA node cell action potential / response to denervation involved in regulation of muscle adaptation ...voltage-gated sodium channel activity involved in AV node cell action potential / voltage-gated sodium channel activity involved in bundle of His cell action potential / voltage-gated sodium channel activity involved in SA node cell action potential / bundle of His cell action potential / AV node cell action potential / sodium channel complex / SA node cell action potential / AV node cell to bundle of His cell communication / membrane depolarization during SA node cell action potential / response to denervation involved in regulation of muscle adaptation / regulation of atrial cardiac muscle cell membrane repolarization / regulation of ventricular cardiac muscle cell membrane depolarization / membrane depolarization during atrial cardiac muscle cell action potential / cardiac ventricle development / regulation of sodium ion transmembrane transport / voltage-gated sodium channel activity involved in Purkinje myocyte action potential / telencephalon development / brainstem development / voltage-gated sodium channel activity involved in cardiac muscle cell action potential / membrane depolarization during AV node cell action potential / membrane depolarization during bundle of His cell action potential / positive regulation of action potential / atrial cardiac muscle cell action potential / membrane depolarization during Purkinje myocyte cell action potential / regulation of atrial cardiac muscle cell membrane depolarization / membrane depolarization during cardiac muscle cell action potential / positive regulation of sodium ion transport / sodium ion import across plasma membrane / ventricular cardiac muscle cell action potential / cardiac muscle cell action potential involved in contraction / membrane depolarization during action potential / voltage-gated sodium channel complex / regulation of ventricular cardiac muscle cell membrane repolarization / regulation of cardiac muscle cell contraction / voltage-gated sodium channel activity / ankyrin binding / positive regulation of heart rate / fibroblast growth factor binding / sodium ion transport / odontogenesis of dentin-containing tooth / nitric-oxide synthase binding / regulation of heart rate by cardiac conduction / membrane depolarization / intercalated disc / neuronal action potential / lateral plasma membrane / sodium ion transmembrane transport / cardiac muscle contraction / T-tubule / cellular response to calcium ion / regulation of heart rate / bioluminescence / cerebellum development / positive regulation of epithelial cell proliferation / generation of precursor metabolites and energy / caveola / response to organic cyclic compound / sarcolemma / Z disc / scaffold protein binding / transmembrane transporter binding / calmodulin binding / protein domain specific binding / axon / ubiquitin protein ligase binding / protein kinase binding / perinuclear region of cytoplasm / enzyme binding / cell surface / endoplasmic reticulum / membrane / plasma membrane Similarity search - Function | |||||||||
Biological species | Rattus norvegicus (Norway rat) Aequorea victoria (jellyfish) | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.5 Å | |||||||||
Authors | Jiang, D. / Shi, H. / Tonggu, L. / Lenaeus, M.J. / Zheng, N. / Catterall, W.A. | |||||||||
Funding support | United States, 2items
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Citation | Journal: Cell / Year: 2020 Title: Structure of the Cardiac Sodium Channel. Authors: Daohua Jiang / Hui Shi / Lige Tonggu / Tamer M Gamal El-Din / Michael J Lenaeus / Yan Zhao / Craig Yoshioka / Ning Zheng / William A Catterall / Abstract: Voltage-gated sodium channel Na1.5 generates cardiac action potentials and initiates the heartbeat. Here, we report structures of Na1.5 at 3.2-3.5 Å resolution. Na1.5 is distinguished from other ...Voltage-gated sodium channel Na1.5 generates cardiac action potentials and initiates the heartbeat. Here, we report structures of Na1.5 at 3.2-3.5 Å resolution. Na1.5 is distinguished from other sodium channels by a unique glycosyl moiety and loss of disulfide-bonding capability at the Naβ subunit-interaction sites. The antiarrhythmic drug flecainide specifically targets the central cavity of the pore. The voltage sensors are partially activated, and the fast-inactivation gate is partially closed. Activation of the voltage sensor of Domain III allows binding of the isoleucine-phenylalanine-methionine (IFM) motif to the inactivation-gate receptor. Asp and Ala, in the selectivity motif DEKA, line the walls of the ion-selectivity filter, whereas Glu and Lys are in positions to accept and release Na ions via a charge-delocalization network. Arrhythmia mutation sites undergo large translocations during gating, providing a potential mechanism for pathogenic effects. Our results provide detailed insights into Na1.5 structure, pharmacology, activation, inactivation, ion selectivity, and arrhythmias. | |||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 6uz3.cif.gz | 250.6 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6uz3.ent.gz | 182.1 KB | Display | PDB format |
PDBx/mmJSON format | 6uz3.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 6uz3_validation.pdf.gz | 1.8 MB | Display | wwPDB validaton report |
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Full document | 6uz3_full_validation.pdf.gz | 1.8 MB | Display | |
Data in XML | 6uz3_validation.xml.gz | 54.2 KB | Display | |
Data in CIF | 6uz3_validation.cif.gz | 77.7 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/uz/6uz3 ftp://data.pdbj.org/pub/pdb/validation_reports/uz/6uz3 | HTTPS FTP |
-Related structure data
Related structure data | 20951MC 6uz0C M: map data used to model this data C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
-Protein , 1 types, 1 molecules A
#1: Protein | Mass: 209037.781 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Rattus norvegicus (Norway rat), (gene. exp.) Aequorea victoria (jellyfish) Gene: Scn5a, GFP / Organ: heart / Plasmid: pEG_BacMam / Cell line (production host): HEK293S / Production host: Mammalian 1 orthobornavirus / References: UniProt: P15389, UniProt: P42212 |
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-Sugars , 3 types, 5 molecules
#2: Polysaccharide | Source method: isolated from a genetically manipulated source #3: Polysaccharide | beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta- ...beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose | Source method: isolated from a genetically manipulated source #4: Sugar | |
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-Non-polymers , 2 types, 16 molecules
#5: Chemical | ChemComp-9Z9 / ( #6: Chemical | ChemComp-6OU / [( |
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-Details
Has ligand of interest | N |
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Has protein modification | Y |
-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: cardiac sodium channel apo structure / Type: COMPLEX / Entity ID: #1 / Source: RECOMBINANT | |||||||||||||||
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Molecular weight | Value: 0.25 MDa / Experimental value: NO | |||||||||||||||
Source (natural) | Organism: Rattus norvegicus (Norway rat) / Organ: heart | |||||||||||||||
Source (recombinant) | Organism: Mammalian 1 orthobornavirus / Strain: HEK293 / Plasmid: pEG_BacMam | |||||||||||||||
Buffer solution | pH: 6 | |||||||||||||||
Buffer component |
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Specimen | Conc.: 4.5 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES Details: This sample include channel protein solubilized with GDN detergent. | |||||||||||||||
Specimen support | Grid material: GOLD / Grid mesh size: 300 divisions/in. / Grid type: UltrAuFoil | |||||||||||||||
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 277 K / Details: waiting for 20s, blot for 2.5-3.5s before plunging |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS Details: Squares on grids were manually screened before data collection |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD / Nominal magnification: 130000 X / Nominal defocus max: 2800 nm / Nominal defocus min: 1200 nm / Calibrated defocus min: 1000 nm / Calibrated defocus max: 3000 nm / Cs: 2.7 mm / C2 aperture diameter: 50 µm / Alignment procedure: COMA FREE |
Specimen holder | Cryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Temperature (max): 103 K / Temperature (min): 95 K |
Image recording | Average exposure time: 8 sec. / Electron dose: 60 e/Å2 / Detector mode: SUPER-RESOLUTION / Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Num. of grids imaged: 6 / Num. of real images: 7400 |
EM imaging optics | Energyfilter name: GIF Bioquantum / Energyfilter slit width: 20 eV |
Image scans | Movie frames/image: 40 / Used frames/image: 1-40 |
-Processing
Software | Name: PHENIX / Version: 1.15.2_3472: / Classification: refinement | ||||||||||||||||||||||||||||||
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EM software |
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Image processing | Details: The images were manually inspected. | ||||||||||||||||||||||||||||||
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||||
Particle selection | Num. of particles selected: 2188972 / Details: particles were autopicked in relion3 | ||||||||||||||||||||||||||||||
Symmetry | Point symmetry: C1 (asymmetric) | ||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 3.5 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 106104 / Num. of class averages: 1 / Symmetry type: POINT | ||||||||||||||||||||||||||||||
Atomic model building | B value: 100 / Protocol: RIGID BODY FIT / Space: REAL | ||||||||||||||||||||||||||||||
Atomic model building | PDB-ID: 6AGF Pdb chain-ID: A / Accession code: 6AGF / Source name: PDB / Type: experimental model | ||||||||||||||||||||||||||||||
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