+Open data
-Basic information
Entry | Database: PDB / ID: 7wfw | ||||||
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Title | Apo human Nav1.8 | ||||||
Components | Sodium channel protein type 10 subunit alpha | ||||||
Keywords | MEMBRANE PROTEIN / Voltage-gated sodium channel / Nav / activation / selectivity | ||||||
Function / homology | Function and homology information bundle of His cell action potential / AV node cell action potential / clathrin complex / voltage-gated sodium channel activity involved in cardiac muscle cell action potential / regulation of atrial cardiac muscle cell membrane depolarization / sensory perception / voltage-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential / cardiac muscle cell action potential involved in contraction / voltage-gated sodium channel complex / membrane depolarization during action potential ...bundle of His cell action potential / AV node cell action potential / clathrin complex / voltage-gated sodium channel activity involved in cardiac muscle cell action potential / regulation of atrial cardiac muscle cell membrane depolarization / sensory perception / voltage-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential / cardiac muscle cell action potential involved in contraction / voltage-gated sodium channel complex / membrane depolarization during action potential / 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 / sodium ion transmembrane transport / regulation of cardiac muscle contraction / neuronal action potential / regulation of heart rate / presynaptic membrane / transmembrane transporter binding / axon / glutamatergic synapse / extracellular exosome / plasma membrane Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.1 Å | ||||||
Authors | Yan, N. / Pan, X.J. / Huang, X.S. / Huang, G.X. | ||||||
Funding support | China, 1items
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Citation | Journal: Proc Natl Acad Sci U S A / Year: 2022 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: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 7wfw.cif.gz | 215.7 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7wfw.ent.gz | 164.9 KB | Display | PDB format |
PDBx/mmJSON format | 7wfw.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7wfw_validation.pdf.gz | 1.5 MB | Display | wwPDB validaton report |
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Full document | 7wfw_full_validation.pdf.gz | 1.6 MB | Display | |
Data in XML | 7wfw_validation.xml.gz | 42.5 KB | Display | |
Data in CIF | 7wfw_validation.cif.gz | 60.3 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/wf/7wfw ftp://data.pdbj.org/pub/pdb/validation_reports/wf/7wfw | HTTPS FTP |
-Related structure data
Related structure data | 32476MC 7we4C 7welC 7wfrC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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1 |
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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.) Homo sapiens (human) / Gene: SCN10A / Production host: Homo sapiens (human) / References: UniProt: Q9Y5Y9 |
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-Sugars , 2 types, 5 molecules
#2: Polysaccharide | 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose Source method: isolated from a genetically manipulated source |
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#3: Sugar | ChemComp-NAG / |
-Non-polymers , 4 types, 17 molecules
#4: Chemical | ChemComp-CLR / #5: Chemical | #6: Chemical | ChemComp-LPE / #7: Chemical | |
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-Details
Has ligand of interest | N |
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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 |
-Sample preparation
Component | Name: sodium channel II / Type: COMPLEX / Entity ID: #1 / 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 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) |
-Processing
Software | Name: PHENIX / Version: 1.18_3855: / Classification: refinement | ||||||||||||||||||||||||
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.1 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 410478 / Symmetry type: POINT | ||||||||||||||||||||||||
Refine LS restraints |
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