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Open data
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Basic information
Entry | Database: PDB / ID: 7w9l | ||||||
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Title | Cryo-EM structure of human Nav1.7(E406K)-beta1-beta2 complex | ||||||
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Function / homology | ![]() corticospinal neuron axon guidance / positive regulation of voltage-gated sodium channel activity / response to pyrethroid / detection of mechanical stimulus involved in sensory perception / voltage-gated sodium channel activity involved in Purkinje myocyte action potential / regulation of sodium ion transmembrane transporter activity / voltage-gated sodium channel activity involved in cardiac muscle cell action potential / voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization / membrane depolarization during Purkinje myocyte cell action potential / regulation of atrial cardiac muscle cell membrane depolarization ...corticospinal neuron axon guidance / positive regulation of voltage-gated sodium channel activity / response to pyrethroid / detection of mechanical stimulus involved in sensory perception / voltage-gated sodium channel activity involved in Purkinje myocyte action potential / regulation of sodium ion transmembrane transporter activity / voltage-gated sodium channel activity involved in cardiac muscle cell action potential / voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization / membrane depolarization during Purkinje myocyte cell action potential / regulation of atrial cardiac muscle cell membrane depolarization / cardiac conduction / membrane depolarization during action potential / ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() Similarity search - Function | ||||||
Biological species | ![]() ![]() | ||||||
Method | ![]() ![]() ![]() | ||||||
![]() | Yan, N. / Huang, G. / Liu, D. / Wei, P. / Shen, H. | ||||||
Funding support | ![]()
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![]() | ![]() Title: High-resolution structures of human Na1.7 reveal gating modulation through α-π helical transition of S6. Authors: Gaoxingyu Huang / Dongliang Liu / Weipeng Wang / Qiurong Wu / Jiaofeng Chen / Xiaojing Pan / Huaizong Shen / Nieng Yan / ![]() Abstract: Na1.7 represents a preeminent target for next-generation analgesics for its critical role in pain sensation. Here we report a 2.2-Å resolution cryo-EM structure of wild-type (WT) Na1.7 complexed ...Na1.7 represents a preeminent target for next-generation analgesics for its critical role in pain sensation. Here we report a 2.2-Å resolution cryo-EM structure of wild-type (WT) Na1.7 complexed with the β1 and β2 subunits that reveals several previously indiscernible cytosolic segments. Reprocessing of the cryo-EM data for our reported structures of Na1.7(E406K) bound to various toxins identifies two distinct conformations of S6, one composed of α helical turns only and the other containing a π helical turn in the middle. The structure of ligand-free Na1.7(E406K), determined at 3.5-Å resolution, is identical to the WT channel, confirming that binding of Huwentoxin IV or Protoxin II to VSD allosterically induces the α → π transition of S6. The local secondary structural shift leads to contraction of the intracellular gate, closure of the fenestration on the interface of repeats I and IV, and rearrangement of the binding site for the fast inactivation motif. | ||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 361.9 KB | Display | ![]() |
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PDB format | ![]() | 288.4 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 32369MC ![]() 7w9kC ![]() 7w9mC ![]() 7w9pC ![]() 7w9tC 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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1 |
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Components
-Protein , 1 types, 1 molecules A
#1: Protein | ![]() Mass: 231211.922 Da / Num. of mol.: 1 / Mutation: E406K Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() |
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-Sodium channel subunit beta- ... , 2 types, 2 molecules BC
#2: Protein | ![]() Mass: 24732.115 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() |
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#3: Protein | ![]() Mass: 24355.859 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() |
-Sugars , 2 types, 8 molecules ![](data/chem/img/NAG.gif)
#4: Polysaccharide | ![]() Source method: isolated from a genetically manipulated source #5: Sugar | ChemComp-NAG / ![]() |
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-Non-polymers , 5 types, 29 molecules ![](data/chem/img/P5S.gif)
![](data/chem/img/Y01.gif)
![](data/chem/img/9Z9.gif)
![](data/chem/img/LPE.gif)
![](data/chem/img/PCW.gif)
![](data/chem/img/Y01.gif)
![](data/chem/img/9Z9.gif)
![](data/chem/img/LPE.gif)
![](data/chem/img/PCW.gif)
#6: Chemical | ![]() #7: Chemical | ChemComp-Y01 / #8: Chemical | ChemComp-9Z9 / ( | #9: Chemical | ChemComp-LPE / #10: Chemical | ChemComp-PCW / |
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-Details
Has ligand of interest | Y |
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-Experimental details
-Experiment
Experiment | Method: ![]() |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: ![]() |
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Sample preparation
Component | Name: Human voltage-gated sodium channel Nav1.7 in complex with auxiliary beta subunits Type: COMPLEX / Entity ID: #1-#3 / Source: RECOMBINANT |
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Molecular weight | Value: 279.99 kDa/nm / Experimental value: NO |
Source (natural) | Organism: ![]() ![]() |
Source (recombinant) | Organism: ![]() ![]() |
Buffer solution | pH: 7.4 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied![]() ![]() |
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![]() |
Image recording | Electron dose: 50 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
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Processing
CTF correction![]() | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
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Symmetry | Point symmetry![]() |
3D reconstruction![]() | Resolution: 3.5 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 1197096 / Symmetry type: POINT |