+Open data
-Basic information
Entry | Database: PDB / ID: 7fbs | ||||||
---|---|---|---|---|---|---|---|
Title | structure of a channel | ||||||
Components | Sodium channel protein type 5 subunit alpha,Sodium channel protein type 5 subunit alpha,Sodium channel protein type 5 subunit alpha,G protein/GFP fusion protein | ||||||
Keywords | MEMBRANE PROTEIN / ion channel / four-domain | ||||||
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 / cardiac ventricle development / regulation of ventricular cardiac muscle cell membrane depolarization / regulation of atrial cardiac muscle cell membrane repolarization / membrane depolarization during atrial cardiac muscle cell action potential / voltage-gated sodium channel activity involved in Purkinje myocyte action potential / regulation of sodium ion transmembrane transport / brainstem development / membrane depolarization during AV node cell action potential / voltage-gated sodium channel activity involved in cardiac muscle 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 / telencephalon development / 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 / regulation of ventricular cardiac muscle cell membrane repolarization / regulation of cardiac muscle cell contraction / voltage-gated sodium channel complex / membrane depolarization during action potential / voltage-gated sodium channel activity / ankyrin binding / sodium ion transport / positive regulation of heart rate / nitric-oxide synthase binding / fibroblast growth factor binding / regulation of heart rate by cardiac conduction / odontogenesis of dentin-containing tooth / membrane depolarization / intercalated disc / sodium ion transmembrane transport / lateral plasma membrane / neuronal action potential / cardiac muscle contraction / T-tubule / cellular response to calcium ion / regulation of heart rate / bioluminescence / cerebellum development / generation of precursor metabolites and energy / caveola / positive regulation of epithelial cell proliferation / response to organic cyclic compound / sarcolemma / Z disc / scaffold protein binding / transmembrane transporter binding / calmodulin binding / symbiont entry into host cell / protein domain specific binding / axon / viral envelope / ubiquitin protein ligase binding / virion attachment to host cell / 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) Recombinant vesicular stomatitis Indiana virus rVSV-G/GFP | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.4 Å | ||||||
Authors | Jiang, D.J. / Catterall, W.A. | ||||||
Funding support | United States, 1items
| ||||||
Citation | Journal: Cell / Year: 2021 Title: Open-state structure and pore gating mechanism of the cardiac sodium channel. Authors: Daohua Jiang / Richard Banh / Tamer M Gamal El-Din / Lige Tonggu / Michael J Lenaeus / Régis Pomès / Ning Zheng / William A Catterall / Abstract: The heartbeat is initiated by voltage-gated sodium channel Na1.5, which opens rapidly and triggers the cardiac action potential; however, the structural basis for pore opening remains unknown. Here, ...The heartbeat is initiated by voltage-gated sodium channel Na1.5, which opens rapidly and triggers the cardiac action potential; however, the structural basis for pore opening remains unknown. Here, we blocked fast inactivation with a mutation and captured the elusive open-state structure. The fast inactivation gate moves away from its receptor, allowing asymmetric opening of pore-lining S6 segments, which bend and rotate at their intracellular ends to dilate the activation gate to ∼10 Å diameter. Molecular dynamics analyses predict physiological rates of Na conductance. The open-state pore blocker propafenone binds in a high-affinity pose, and drug-access pathways are revealed through the open activation gate and fenestrations. Comparison with mutagenesis results provides a structural map of arrhythmia mutations that target the activation and fast inactivation gates. These results give atomic-level insights into molecular events that underlie generation of the action potential, open-state drug block, and fast inactivation of cardiac sodium channels, which initiate the heartbeat. | ||||||
History |
|
-Structure visualization
Movie |
Movie viewer |
---|---|
Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 7fbs.cif.gz | 230.9 KB | Display | PDBx/mmCIF format |
---|---|---|---|---|
PDB format | pdb7fbs.ent.gz | 179 KB | Display | PDB format |
PDBx/mmJSON format | 7fbs.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7fbs_validation.pdf.gz | 1.3 MB | Display | wwPDB validaton report |
---|---|---|---|---|
Full document | 7fbs_full_validation.pdf.gz | 1.3 MB | Display | |
Data in XML | 7fbs_validation.xml.gz | 49.1 KB | Display | |
Data in CIF | 7fbs_validation.cif.gz | 71.5 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/fb/7fbs ftp://data.pdbj.org/pub/pdb/validation_reports/fb/7fbs | HTTPS FTP |
-Related structure data
Related structure data | 31519MC M: map data used to model this data C: citing same article (ref.) |
---|---|
Similar structure data |
-Links
-Assembly
Deposited unit |
|
---|---|
1 |
|
-Components
#1: Protein | Mass: 209030.625 Da / Num. of mol.: 1 / Mutation: I1487Q,F1488Q,M1489Q Source method: isolated from a genetically manipulated source Source: (gene. exp.) Rattus norvegicus (Norway rat), (gene. exp.) Recombinant vesicular stomatitis Indiana virus rVSV-G/GFP Gene: Scn5a, G, GFP / Production host: Mammalian 1 orthobornavirus / References: UniProt: P15389, UniProt: B7UCZ6 | ||||||||
---|---|---|---|---|---|---|---|---|---|
#2: Sugar | #3: Chemical | ChemComp-6OU / [( #4: Chemical | ChemComp-4Y4 / | #5: 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: sodium channel with four homologous domains / Type: COMPLEX / Entity ID: #1 / Source: RECOMBINANT | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Molecular weight | Value: 0.25 MDa / Experimental value: NO | ||||||||||||
Source (natural) |
| ||||||||||||
Source (recombinant) |
| ||||||||||||
Buffer solution | pH: 6 | ||||||||||||
Specimen | Conc.: 5 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||
Specimen support | Grid material: GOLD / Grid mesh size: 300 divisions/in. | ||||||||||||
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: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD / Cs: 2.7 mm |
Specimen holder | Cryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Image recording | Electron dose: 60 e/Å2 / Detector mode: SUPER-RESOLUTION / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
EM imaging optics | Energyfilter name: GIF Quantum ER / Energyfilter slit width: 20 eV |
-Processing
Software | Name: PHENIX / Version: 1.17.1_3660: / Classification: refinement | ||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.4 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 287306 / Symmetry type: POINT | ||||||||||||||||||||||||
Atomic model building | Protocol: RIGID BODY FIT / Space: REAL | ||||||||||||||||||||||||
Refine LS restraints |
|