+Open data
-Basic information
Entry | Database: PDB / ID: 6j8e | |||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Title | Human Nav1.2-beta2-KIIIA ternary complex | |||||||||||||||||||||||||||
Components |
| |||||||||||||||||||||||||||
Keywords | MEMBRANE PROTEIN/TOXIN / transmembrane protein / MEMBRANE PROTEIN / MEMBRANE PROTEIN-TOXIN complex | |||||||||||||||||||||||||||
Function / homology | Function and homology information response to pyrethroid / voltage-gated sodium channel activity involved in cardiac muscle cell action potential / regulation of sodium ion transmembrane transporter activity / voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization / intrinsic apoptotic signaling pathway in response to osmotic stress / nerve development / regulation of atrial cardiac muscle cell membrane depolarization / paranode region of axon / membrane depolarization during cardiac muscle cell action potential / dentate gyrus development ...response to pyrethroid / voltage-gated sodium channel activity involved in cardiac muscle cell action potential / regulation of sodium ion transmembrane transporter activity / voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization / intrinsic apoptotic signaling pathway in response to osmotic stress / nerve development / regulation of atrial cardiac muscle cell membrane depolarization / paranode region of axon / membrane depolarization during cardiac muscle cell action potential / dentate gyrus development / node of Ranvier / cardiac muscle cell action potential involved in contraction / voltage-gated sodium channel complex / Interaction between L1 and Ankyrins / voltage-gated sodium channel activity / sodium ion transport / Phase 0 - rapid depolarisation / regulation of heart rate by cardiac conduction / intercalated disc / neuronal action potential / sodium ion transmembrane transport / sodium channel regulator activity / cardiac muscle contraction / T-tubule / myelination / determination of adult lifespan / memory / Sensory perception of sweet, bitter, and umami (glutamate) taste / cellular response to hypoxia / nervous system development / presynaptic membrane / gene expression / response to heat / chemical synaptic transmission / neuron apoptotic process / toxin activity / calmodulin binding / axon / glutamatergic synapse / synapse / extracellular region / membrane / plasma membrane Similarity search - Function | |||||||||||||||||||||||||||
Biological species | Homo sapiens (human) Conus kinoshitai (invertebrata) | |||||||||||||||||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3 Å | |||||||||||||||||||||||||||
Authors | Pan, X. / Li, Z. / Huang, X. / Huang, G. / Yan, N. | |||||||||||||||||||||||||||
Funding support | China, 8items
| |||||||||||||||||||||||||||
Citation | Journal: Science / Year: 2019 Title: Molecular basis for pore blockade of human Na channel Na1.2 by the μ-conotoxin KIIIA. Authors: Xiaojing Pan / Zhangqiang Li / Xiaoshuang Huang / Gaoxingyu Huang / Shuai Gao / Huaizong Shen / Lei Liu / Jianlin Lei / Nieng Yan / Abstract: The voltage-gated sodium channel Na1.2 is responsible for the initiation and propagation of action potentials in the central nervous system. We report the cryo-electron microscopy structure of human ...The voltage-gated sodium channel Na1.2 is responsible for the initiation and propagation of action potentials in the central nervous system. We report the cryo-electron microscopy structure of human Na1.2 bound to a peptidic pore blocker, the μ-conotoxin KIIIA, in the presence of an auxiliary subunit, β2, to an overall resolution of 3.0 angstroms. The immunoglobulin domain of β2 interacts with the shoulder of the pore domain through a disulfide bond. The 16-residue KIIIA interacts with the extracellular segments in repeats I to III, placing Lys at the entrance to the selectivity filter. Many interacting residues are specific to Na1.2, revealing a molecular basis for KIIIA specificity. The structure establishes a framework for the rational design of subtype-specific blockers for Na channels. | |||||||||||||||||||||||||||
History |
|
-Structure visualization
Movie |
Movie viewer |
---|---|
Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 6j8e.cif.gz | 288.9 KB | Display | PDBx/mmCIF format |
---|---|---|---|---|
PDB format | pdb6j8e.ent.gz | 219.5 KB | Display | PDB format |
PDBx/mmJSON format | 6j8e.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 6j8e_validation.pdf.gz | 1.1 MB | Display | wwPDB validaton report |
---|---|---|---|---|
Full document | 6j8e_full_validation.pdf.gz | 1.1 MB | Display | |
Data in XML | 6j8e_validation.xml.gz | 43.2 KB | Display | |
Data in CIF | 6j8e_validation.cif.gz | 63.9 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/j8/6j8e ftp://data.pdbj.org/pub/pdb/validation_reports/j8/6j8e | HTTPS FTP |
-Related structure data
Related structure data | 9780MC M: map data used to model this data C: citing same article (ref.) |
---|---|
Similar structure data |
-Links
-Assembly
Deposited unit |
|
---|---|
1 |
|
-Components
-Sodium channel ... , 2 types, 2 molecules CA
#1: Protein | Mass: 14267.261 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 |
---|---|
#2: Protein | Mass: 232800.172 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: SCN2A, NAC2, SCN2A1, SCN2A2 / Production host: Homo sapiens (human) / References: UniProt: Q99250 |
-Protein/peptide , 1 types, 1 molecules D
#3: Protein/peptide | Mass: 1895.220 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) Conus kinoshitai (invertebrata) / References: UniProt: P0C195 |
---|
-Sugars , 3 types, 4 molecules
#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 | ||
---|---|---|---|
#5: Polysaccharide | #6: Sugar | ChemComp-NAG / | |
-Non-polymers , 2 types, 2 molecules
#7: Chemical | ChemComp-9Z9 / ( |
---|---|
#8: Chemical | ChemComp-NA / |
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
---|---|
EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component |
| ||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Molecular weight | Value: 252 kDa/nm / Experimental value: YES | ||||||||||||||||||||||||
Source (natural) |
| ||||||||||||||||||||||||
Source (recombinant) | Organism: Homo sapiens (human) | ||||||||||||||||||||||||
Buffer solution | pH: 5.9 | ||||||||||||||||||||||||
Specimen | Conc.: 1 mg/ml / 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 |
---|---|
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 |
Image recording | Electron dose: 48 e/Å2 / Detector mode: SUPER-RESOLUTION / Film or detector model: GATAN K2 QUANTUM (4k x 4k) |
-Processing
CTF correction | Type: PHASE FLIPPING ONLY |
---|---|
3D reconstruction | Resolution: 3 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 200275 / Symmetry type: POINT |