+Open data
-Basic information
Entry | Database: PDB / ID: 8xmo | ||||||
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Title | Voltage-gated sodium channel Nav1.7 variant M4 | ||||||
Components |
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Keywords | MEMBRANE PROTEIN / Voltage-gated sodium channel | ||||||
Function / homology | Function and homology information 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 cardiac muscle cell action potential / membrane depolarization during Purkinje myocyte cell action potential / voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization / regulation of atrial cardiac muscle cell membrane depolarization / cardiac conduction / regulation of sodium ion transmembrane transport ...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 cardiac muscle cell action potential / membrane depolarization during Purkinje myocyte cell action potential / voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization / regulation of atrial cardiac muscle cell membrane depolarization / cardiac conduction / regulation of sodium ion transmembrane transport / membrane depolarization during cardiac muscle cell action potential / positive regulation of sodium ion transport / node of Ranvier / sodium channel inhibitor activity / membrane depolarization during action potential / voltage-gated sodium channel complex / cardiac muscle cell action potential involved in contraction / locomotion / regulation of ventricular cardiac muscle cell membrane repolarization / neuronal action potential propagation / Interaction between L1 and Ankyrins / voltage-gated sodium channel activity / sodium ion transport / behavioral response to pain / Phase 0 - rapid depolarisation / regulation of heart rate by cardiac conduction / detection of temperature stimulus involved in sensory perception of pain / membrane depolarization / intercalated disc / sodium channel regulator activity / sodium ion transmembrane transport / cardiac muscle contraction / T-tubule / sensory perception of pain / post-embryonic development / axon guidance / response to toxic substance / positive regulation of neuron projection development / Sensory perception of sweet, bitter, and umami (glutamate) taste / circadian rhythm / nervous system development / gene expression / response to heat / chemical synaptic transmission / perikaryon / transmembrane transporter binding / cell adhesion / inflammatory response / axon / synapse / extracellular region / plasma membrane Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.39 Å | ||||||
Authors | Yan, N. / Li, Z. / Wu, Q. / Huang, G. | ||||||
Funding support | China, 1items
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Citation | Journal: Proc Natl Acad Sci U S A / Year: 2024 Title: Dissection of the structure-function relationship of Na channels. Authors: Zhangqiang Li / Qiurong Wu / Gaoxingyu Huang / Xueqin Jin / Jiaao Li / Xiaojing Pan / Nieng Yan / Abstract: Voltage-gated sodium channels (Na) undergo conformational shifts in response to membrane potential changes, a mechanism known as the electromechanical coupling. To delineate the structure-function ...Voltage-gated sodium channels (Na) undergo conformational shifts in response to membrane potential changes, a mechanism known as the electromechanical coupling. To delineate the structure-function relationship of human Na channels, we have performed systematic structural analysis using human Na1.7 as a prototype. Guided by the structural differences between wild-type (WT) Na1.7 and an eleven mutation-containing variant, designated Na1.7-M11, we generated three additional intermediate mutants and solved their structures at overall resolutions of 2.9-3.4 Å. The mutant with nine-point mutations in the pore domain (PD), named Na1.7-M9, has a reduced cavity volume and a sealed gate, with all voltage-sensing domains (VSDs) remaining up. Structural comparison of WT and Na1.7-M9 pinpoints two residues that may be critical to the tightening of the PD. However, the variant containing these two mutations, Na1.7-M2, or even in combination with two additional mutations in the VSDs, named Na1.7-M4, failed to tighten the PD. Our structural analysis reveals a tendency of PD contraction correlated with the right shift of the static inactivation I-V curves. We predict that the channel in the resting state should have a "tight" PD with down VSDs. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8xmo.cif.gz | 329.3 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8xmo.ent.gz | 249.8 KB | Display | PDB format |
PDBx/mmJSON format | 8xmo.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8xmo_validation.pdf.gz | 1.8 MB | Display | wwPDB validaton report |
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Full document | 8xmo_full_validation.pdf.gz | 1.9 MB | Display | |
Data in XML | 8xmo_validation.xml.gz | 60.9 KB | Display | |
Data in CIF | 8xmo_validation.cif.gz | 88.8 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/xm/8xmo ftp://data.pdbj.org/pub/pdb/validation_reports/xm/8xmo | HTTPS FTP |
-Related structure data
Related structure data | 38484MC 8xmmC 8xmnC 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
-Sodium channel subunit beta- ... , 2 types, 2 molecules CB
#1: Protein | Mass: 25979.600 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: SCN2B, UNQ326/PRO386 / Cell line (production host): HEK293 / Production host: Homo sapiens (human) / References: UniProt: O60939 |
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#3: Protein | Mass: 26355.857 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: SCN1B / Cell line (production host): HEK293 / Production host: Homo sapiens (human) / References: UniProt: Q07699 |
-Protein , 1 types, 1 molecules A
#2: Protein | Mass: 231392.172 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: SCN9A, NENA / Cell line (production host): HEK293 / Production host: Homo sapiens (human) / References: UniProt: Q15858 |
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-Sugars , 2 types, 8 molecules
#4: Polysaccharide | Source method: isolated from a genetically manipulated source #5: Sugar | ChemComp-NAG / |
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-Non-polymers , 2 types, 12 molecules
#6: Chemical | ChemComp-LPE / #7: Chemical | ChemComp-PCW / |
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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: Voltage-gated sodium channel Nav1.7-M4 / Type: COMPLEX / Entity ID: #1-#3 / 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
EM software | Name: PHENIX / Version: 1.18_3855: / Category: model refinement | ||||||||||||||||||||||||
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.39 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 181009 / Symmetry type: POINT | ||||||||||||||||||||||||
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