+Open data
-Basic information
Entry | Database: PDB / ID: 7dtd | ||||||
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Title | Voltage-gated sodium channel Nav1.1 and beta4 | ||||||
Components |
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Keywords | MEMBRANE PROTEIN / Voltage-gated sodium channel | ||||||
Function / homology | Function and homology information AV node cell action potential / membrane depolarization during action potential / voltage-gated sodium channel activity involved in cardiac muscle cell action potential / regulation of sodium ion transmembrane transporter activity / voltage-gated monoatomic ion channel activity / voltage-gated sodium channel complex / membrane depolarization during cardiac muscle cell action potential / positive regulation of sodium ion transport / cardiac muscle cell action potential involved in contraction / voltage-gated sodium channel activity ...AV node cell action potential / membrane depolarization during action potential / voltage-gated sodium channel activity involved in cardiac muscle cell action potential / regulation of sodium ion transmembrane transporter activity / voltage-gated monoatomic ion channel activity / voltage-gated sodium channel complex / membrane depolarization during cardiac muscle cell action potential / positive regulation of sodium ion transport / cardiac muscle cell action potential involved in contraction / voltage-gated sodium channel activity / regulation of ventricular cardiac muscle cell membrane repolarization / regulation of monoatomic ion transmembrane transport / Interaction between L1 and Ankyrins / sodium ion transport / regulation of heart rate by cardiac conduction / Phase 0 - rapid depolarisation / neuronal action potential / sodium ion transmembrane transport / sodium channel regulator activity / intercalated disc / detection of mechanical stimulus involved in sensory perception of pain / monoatomic cation channel activity / cardiac muscle contraction / establishment of localization in cell / Sensory perception of sweet, bitter, and umami (glutamate) taste / Z disc / transmembrane transporter binding / nuclear body / axon / nucleoplasm / plasma membrane Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.3 Å | ||||||
Authors | Yan, N. / Pan, X. / Li, Z. / Huang, G. | ||||||
Funding support | China, 1items
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Citation | Journal: Proc Natl Acad Sci U S A / Year: 2021 Title: Comparative structural analysis of human Na1.1 and Na1.5 reveals mutational hotspots for sodium channelopathies. Authors: Xiaojing Pan / Zhangqiang Li / Xueqin Jin / Yanyu Zhao / Gaoxingyu Huang / Xiaoshuang Huang / Zilin Shen / Yong Cao / Mengqiu Dong / Jianlin Lei / Nieng Yan / Abstract: Among the nine subtypes of human voltage-gated sodium (Na) channels, the brain and cardiac isoforms, Na1.1 and Na1.5, each carry more than 400 missense mutations respectively associated with epilepsy ...Among the nine subtypes of human voltage-gated sodium (Na) channels, the brain and cardiac isoforms, Na1.1 and Na1.5, each carry more than 400 missense mutations respectively associated with epilepsy and cardiac disorders. High-resolution structures are required for structure-function relationship dissection of the disease variants. We report the cryo-EM structures of the full-length human Na1.1-β4 complex at 3.3 Å resolution here and the Na1.5-E1784K variant in the accompanying paper. Up to 341 and 261 disease-related missense mutations in Na1.1 and Na1.5, respectively, are resolved. Comparative structural analysis reveals several clusters of disease mutations that are common to both Na1.1 and Na1.5. Among these, the majority of mutations on the extracellular loops above the pore domain and the supporting segments for the selectivity filter may impair structural integrity, while those on the pore domain and the voltage-sensing domains mostly interfere with electromechanical coupling and fast inactivation. Our systematic structural delineation of these mutations provides important insight into their pathogenic mechanism, which will facilitate the development of precise therapeutic interventions against various sodium channelopathies. | ||||||
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 | 7dtd.cif.gz | 256.7 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7dtd.ent.gz | 197.2 KB | Display | PDB format |
PDBx/mmJSON format | 7dtd.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/dt/7dtd ftp://data.pdbj.org/pub/pdb/validation_reports/dt/7dtd | HTTPS FTP |
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-Related structure data
Related structure data | 30851MC 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
#1: Protein | Mass: 25000.980 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: SCN4B / Production host: Homo sapiens (human) / References: UniProt: Q8IWT1 | ||||
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#2: Protein | Mass: 233796.141 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: SCN1A, NAC1, SCN1 / Production host: Homo sapiens (human) / References: UniProt: P35498 | ||||
#3: Sugar | ChemComp-NAG / #4: Chemical | ChemComp-9Z9 / ( | Has ligand of interest | N | |
-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: Voltage-gated sodium channelSodium channel / Type: COMPLEX / Entity ID: #1-#2 / Source: RECOMBINANT |
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Source (natural) | Organism: Homo sapiens (human) |
Source (recombinant) | Organism: Homo sapiens (human) |
Buffer solution | pH: 7.5 |
Specimen | 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 |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELDBright-field microscopy |
Image recording | Electron dose: 48 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
-Processing
CTF correction | Type: PHASE FLIPPING ONLY |
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3D reconstruction | Resolution: 3.3 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 133127 / Symmetry type: POINT |