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Open data
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Basic information
Entry | Database: PDB / ID: 7wel | ||||||
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Title | Human Nav1.8 with A-803467, class II | ||||||
![]() | Sodium channel protein type 10 subunit alpha | ||||||
![]() | MEMBRANE PROTEIN / Voltage-gated sodium channel / Nav / activation / selectivity | ||||||
Function / homology | ![]() bundle of His cell action potential / AV node cell action potential / clathrin complex / regulation of atrial cardiac muscle cell membrane depolarization / sensory perception / voltage-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential / membrane depolarization during action potential / cardiac muscle cell action potential involved in contraction / voltage-gated sodium channel complex / regulation of monoatomic ion transmembrane transport ...bundle of His cell action potential / AV node cell action potential / clathrin complex / regulation of atrial cardiac muscle cell membrane depolarization / sensory perception / voltage-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential / membrane depolarization during action potential / cardiac muscle cell action potential involved in contraction / voltage-gated sodium channel complex / regulation of monoatomic ion transmembrane transport / Interaction between L1 and Ankyrins / voltage-gated sodium channel activity / Phase 0 - rapid depolarisation / odontogenesis of dentin-containing tooth / regulation of cardiac muscle contraction / sodium ion transmembrane transport / regulation of heart rate / presynaptic membrane / transmembrane transporter binding / axon / glutamatergic synapse / extracellular exosome / plasma membrane Similarity search - Function | ||||||
Biological species | ![]() | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.2 Å | ||||||
![]() | Yan, N. / Pan, X.J. / Huang, X.S. / Huang, G.X. | ||||||
Funding support | ![]()
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![]() | ![]() Title: Structural basis for high-voltage activation and subtype-specific inhibition of human Na1.8. Authors: Xiaoshuang Huang / Xueqin Jin / Gaoxingyu Huang / Jian Huang / Tong Wu / Zhangqiang Li / Jiaofeng Chen / Fang Kong / Xiaojing Pan / Nieng Yan / ![]() Abstract: The dorsal root ganglia-localized voltage-gated sodium (Na) channel Na1.8 represents a promising target for developing next-generation analgesics. A prominent characteristic of Na1.8 is the ...The dorsal root ganglia-localized voltage-gated sodium (Na) channel Na1.8 represents a promising target for developing next-generation analgesics. A prominent characteristic of Na1.8 is the requirement of more depolarized membrane potential for activation. Here we present the cryogenic electron microscopy structures of human Na1.8 alone and bound to a selective pore blocker, A-803467, at overall resolutions of 2.7 to 3.2 Å. The first voltage-sensing domain (VSD) displays three different conformations. Structure-guided mutagenesis identified the extracellular interface between VSD and the pore domain (PD) to be a determinant for the high-voltage dependence of activation. A-803467 was clearly resolved in the central cavity of the PD, clenching S6. Our structure-guided functional characterizations show that two nonligand binding residues, Thr397 on S6 and Gly1406 on S6, allosterically modulate the channel's sensitivity to A-803467. Comparison of available structures of human Na channels suggests the extracellular loop region to be a potential site for developing subtype-specific pore-blocking biologics. | ||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 239.9 KB | Display | ![]() |
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PDB format | ![]() | 187.1 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 32451MC ![]() 7we4C ![]() 7wfrC ![]() 7wfwC M: map data used to model this data C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
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Assembly
Deposited unit | ![]()
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Components
-Protein , 1 types, 1 molecules A
#1: Protein | Mass: 220903.500 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
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-Sugars , 2 types, 5 molecules ![](data/chem/img/NAG.gif)
#2: Polysaccharide | Source method: isolated from a genetically manipulated source #3: Sugar | |
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-Non-polymers , 5 types, 27 molecules ![](data/chem/img/95T.gif)
![](data/chem/img/CLR.gif)
![](data/chem/img/PCW.gif)
![](data/chem/img/LPE.gif)
![](data/chem/img/P5S.gif)
![](data/chem/img/CLR.gif)
![](data/chem/img/PCW.gif)
![](data/chem/img/LPE.gif)
![](data/chem/img/P5S.gif)
#4: Chemical | ChemComp-95T / | ||||||
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#5: Chemical | ChemComp-CLR / #6: Chemical | ChemComp-PCW / #7: Chemical | ChemComp-LPE / #8: Chemical | |
-Details
Has ligand of interest | Y |
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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: sodium channel II / Type: COMPLEX / Entity ID: #1 / Source: RECOMBINANT |
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Source (natural) | Organism: ![]() |
Source (recombinant) | Organism: ![]() |
Buffer solution | pH: 7.5 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
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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 defocus max: 1800 nm / Nominal defocus min: 1500 nm |
Image recording | Electron dose: 50 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
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Processing
Software | Name: PHENIX / Version: 1.19.2_4158: / Classification: refinement | ||||||||||||||||||||||||
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.2 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 141848 / Symmetry type: POINT | ||||||||||||||||||||||||
Refine LS restraints |
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