+Open data
-Basic information
Entry | Database: PDB / ID: 7xvf | |||||||||
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Title | Nav1.7 mutant class2 | |||||||||
Components |
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Keywords | MEMBRANE PROTEIN / action potential | |||||||||
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 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 cardiac muscle cell action potential / positive regulation of sodium ion transport / node of Ranvier / membrane depolarization during action potential / cardiac muscle cell action potential involved in contraction / voltage-gated sodium channel complex / regulation of ventricular cardiac muscle cell membrane repolarization / locomotion / sodium channel inhibitor activity / 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 / membrane depolarization / detection of temperature stimulus involved in sensory perception of pain / intercalated disc / sodium channel regulator activity / sodium ion transmembrane transport / neuronal action potential / cardiac muscle contraction / sensory perception of pain / T-tubule / post-embryonic development / axon guidance / response to toxic substance / Sensory perception of sweet, bitter, and umami (glutamate) taste / positive regulation of neuron projection development / 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: 2.8 Å | |||||||||
Authors | Huang, G. / Wu, Q. / Li, Z. / Pan, X. / Yan, N. | |||||||||
Funding support | United States, China, 2items
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Citation | Journal: Proc Natl Acad Sci U S A / Year: 2022 Title: Unwinding and spiral sliding of S4 and domain rotation of VSD during the electromechanical coupling in Na1.7. Authors: Gaoxingyu Huang / Qiurong Wu / Zhangqiang Li / Xueqin Jin / Xiaoshuang Huang / Tong Wu / Xiaojing Pan / Nieng Yan / Abstract: Voltage-gated sodium (Na) channel Na1.7 has been targeted for the development of nonaddictive pain killers. Structures of Na1.7 in distinct functional states will offer an advanced mechanistic ...Voltage-gated sodium (Na) channel Na1.7 has been targeted for the development of nonaddictive pain killers. Structures of Na1.7 in distinct functional states will offer an advanced mechanistic understanding and aid drug discovery. Here we report the cryoelectron microscopy analysis of a human Na1.7 variant that, with 11 rationally introduced point mutations, has a markedly right-shifted activation voltage curve with V reaching 69 mV. The voltage-sensing domain in the first repeat (VSD) in a 2.7-Å resolution structure displays a completely down (deactivated) conformation. Compared to the structure of WT Na1.7, three gating charge (GC) residues in VSD are transferred to the cytosolic side through a combination of helix unwinding and spiral sliding of S4 and ∼20° domain rotation. A conserved WNФФD motif on the cytoplasmic end of S3 stabilizes the down conformation of VSD. One GC residue is transferred in VSD mainly through helix sliding. Accompanying GC transfer in VSD and VSD, rearrangement and contraction of the intracellular gate is achieved through concerted movements of adjacent segments, including S4-5, S4-5, S5, and all S6 segments. Our studies provide important insight into the electromechanical coupling mechanism of the single-chain voltage-gated ion channels and afford molecular interpretations for a number of pain-associated mutations whose pathogenic mechanism cannot be revealed from previously reported Na structures. | |||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 7xvf.cif.gz | 334.4 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7xvf.ent.gz | 257.3 KB | Display | PDB format |
PDBx/mmJSON format | 7xvf.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/xv/7xvf ftp://data.pdbj.org/pub/pdb/validation_reports/xv/7xvf | HTTPS FTP |
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-Related structure data
Related structure data | 33485MC 7xveC C: citing same article (ref.) M: map data used to model this data |
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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: 230599.281 Da / Num. of mol.: 1 Mutation: E156K,G779R,L866F,T870M,A874F,V947F,M952F,V953F,V1438I,V1439F,G1454C Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: SCN9A, NENA / Production host: Homo sapiens (human) / References: UniProt: Q15858 |
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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.) Homo sapiens (human) / Gene: SCN1B / Production host: Homo sapiens (human) / References: UniProt: Q07699 |
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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.) Homo sapiens (human) / Gene: SCN2B, UNQ326/PRO386 / Production host: Homo sapiens (human) / References: UniProt: O60939 |
-Sugars , 2 types, 9 molecules
#4: Polysaccharide | #5: Sugar | ChemComp-NAG / |
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-Non-polymers , 6 types, 31 molecules
#6: Chemical | ChemComp-Y01 / #7: Chemical | ChemComp-CLR / | #8: Chemical | ChemComp-LPE / #9: Chemical | ChemComp-1PW / ( | #10: Chemical | ChemComp-PCW / #11: Chemical | ChemComp-P5S / | |
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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: alpha1-beta1-beta2 ternary complex / Type: COMPLEX / Entity ID: #1-#3 / Source: RECOMBINANT |
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Molecular weight | Value: 0.3 MDa / Experimental value: YES |
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 FIELDBright-field microscopy / 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
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
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Symmetry | Point symmetry: C1 (asymmetric) |
3D reconstruction | Resolution: 2.8 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 394163 / Symmetry type: POINT |