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- PDB-8gz2: Cryo-EM structure of human NaV1.6/beta1/beta2-4,9-anhydro-tetrodotoxin -
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Open data
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Basic information
Entry | Database: PDB / ID: 8gz2 | ||||||
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Title | Cryo-EM structure of human NaV1.6/beta1/beta2-4,9-anhydro-tetrodotoxin | ||||||
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![]() | MEMBRANE PROTEIN / ion channal | ||||||
Function / homology | ![]() corticospinal neuron axon guidance / positive regulation of voltage-gated sodium channel activity / response to pyrethroid / 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 / sodium ion binding / axon initial segment ...corticospinal neuron axon guidance / positive regulation of voltage-gated sodium channel activity / response to pyrethroid / 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 / sodium ion binding / axon initial segment / regulation of atrial cardiac muscle cell membrane depolarization / cardiac conduction / membrane depolarization during cardiac muscle cell action potential / positive regulation of sodium ion transport / peripheral nervous system development / node of Ranvier / cardiac muscle cell action potential involved in contraction / regulation of ventricular cardiac muscle cell membrane repolarization / locomotion / sodium channel inhibitor activity / voltage-gated sodium channel complex / neuronal action potential propagation / membrane depolarization during action potential / Interaction between L1 and Ankyrins / parallel fiber to Purkinje cell synapse / voltage-gated sodium channel activity / optic nerve development / sodium ion transport / Phase 0 - rapid depolarisation / regulation of heart rate by cardiac conduction / membrane depolarization / intercalated disc / sodium ion transmembrane transport / sodium channel regulator activity / neuronal action potential / presynaptic active zone membrane / cardiac muscle contraction / T-tubule / myelination / postsynaptic density membrane / axon guidance / Sensory perception of sweet, bitter, and umami (glutamate) taste / positive regulation of neuron projection development / Z disc / cell junction / nervous system development / gene expression / response to heat / cytoplasmic vesicle / chemical synaptic transmission / perikaryon / transmembrane transporter binding / cell adhesion / axon / glutamatergic synapse / synapse / extracellular region / ATP binding / membrane / plasma membrane Similarity search - Function | ||||||
Biological species | ![]() | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.3 Å | ||||||
![]() | Li, Y. / Jiang, D. | ||||||
Funding support | ![]()
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![]() | ![]() Title: Structure of human Na1.6 channel reveals Na selectivity and pore blockade by 4,9-anhydro-tetrodotoxin. Authors: Yue Li / Tian Yuan / Bo Huang / Feng Zhou / Chao Peng / Xiaojing Li / Yunlong Qiu / Bei Yang / Yan Zhao / Zhuo Huang / Daohua Jiang / ![]() Abstract: The sodium channel Na1.6 is widely expressed in neurons of the central and peripheral nervous systems, which plays a critical role in regulating neuronal excitability. Dysfunction of Na1.6 has been ...The sodium channel Na1.6 is widely expressed in neurons of the central and peripheral nervous systems, which plays a critical role in regulating neuronal excitability. Dysfunction of Na1.6 has been linked to epileptic encephalopathy, intellectual disability and movement disorders. Here we present cryo-EM structures of human Na1.6/β1/β2 alone and complexed with a guanidinium neurotoxin 4,9-anhydro-tetrodotoxin (4,9-ah-TTX), revealing molecular mechanism of Na1.6 inhibition by the blocker. The apo-form structure reveals two potential Na binding sites within the selectivity filter, suggesting a possible mechanism for Na selectivity and conductance. In the 4,9-ah-TTX bound structure, 4,9-ah-TTX binds to a pocket similar to the tetrodotoxin (TTX) binding site, which occupies the Na binding sites and completely blocks the channel. Molecular dynamics simulation results show that subtle conformational differences in the selectivity filter affect the affinity of TTX analogues. Taken together, our results provide important insights into Na1.6 structure, ion conductance, and inhibition. | ||||||
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 298.7 KB | Display | ![]() |
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PDB format | ![]() | 230.8 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 1.5 MB | Display | ![]() |
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Full document | ![]() | 1.5 MB | Display | |
Data in XML | ![]() | 52.5 KB | Display | |
Data in CIF | ![]() | 76.7 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 34388MC ![]() 8gz1C 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
-Sodium channel subunit beta- ... , 2 types, 2 molecules DC
#1: 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.) ![]() ![]() |
-Protein / Non-polymers , 2 types, 2 molecules B![](data/chem/img/WMK.gif)
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#2: Protein | Mass: 225520.609 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
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#6: Chemical | ChemComp-WMK / ( |
-Sugars , 2 types, 7 molecules ![](data/chem/img/NAG.gif)
#4: 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 #5: Sugar | |
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-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: Structure of human voltage-gated sodium channel Nav1.6 in complex with auxiliary beta subunits Type: COMPLEX / Entity ID: #1-#3 / 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: 2200 nm / Nominal defocus min: 1200 nm / Cs: 2.7 mm |
Image recording | Electron dose: 9.2 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
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Processing
Software | Name: PHENIX / Version: 1.18.2_3874: / Classification: refinement | ||||||||||||||||||||||||
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CTF correction | Type: PHASE FLIPPING ONLY | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.3 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 76448 / Symmetry type: POINT | ||||||||||||||||||||||||
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