+Open data
-Basic information
Entry | Database: PDB / ID: 7byl | ||||||
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Title | Cryo-EM structure of human KCNQ4 | ||||||
Components |
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Keywords | MEMBRANE PROTEIN / KCNQ / Channel / Calmodulin / PIP2 | ||||||
Function / homology | Function and homology information Voltage gated Potassium channels / Sensory processing of sound by outer hair cells of the cochlea / Sensory processing of sound by inner hair cells of the cochlea / negative regulation of high voltage-gated calcium channel activity / inner ear morphogenesis / positive regulation of cyclic-nucleotide phosphodiesterase activity / negative regulation of calcium ion export across plasma membrane / regulation of cardiac muscle cell action potential / positive regulation of ryanodine-sensitive calcium-release channel activity / regulation of cell communication by electrical coupling involved in cardiac conduction ...Voltage gated Potassium channels / Sensory processing of sound by outer hair cells of the cochlea / Sensory processing of sound by inner hair cells of the cochlea / negative regulation of high voltage-gated calcium channel activity / inner ear morphogenesis / positive regulation of cyclic-nucleotide phosphodiesterase activity / negative regulation of calcium ion export across plasma membrane / regulation of cardiac muscle cell action potential / positive regulation of ryanodine-sensitive calcium-release channel activity / regulation of cell communication by electrical coupling involved in cardiac conduction / negative regulation of peptidyl-threonine phosphorylation / negative regulation of ryanodine-sensitive calcium-release channel activity / protein phosphatase activator activity / voltage-gated potassium channel activity / : / adenylate cyclase binding / potassium channel activity / catalytic complex / detection of calcium ion / regulation of cardiac muscle contraction / regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion / regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum / basal plasma membrane / : / titin binding / regulation of calcium-mediated signaling / positive regulation of protein autophosphorylation / voltage-gated potassium channel complex / sperm midpiece / potassium ion transmembrane transport / calcium channel complex / substantia nigra development / adenylate cyclase activator activity / regulation of heart rate / sarcomere / protein serine/threonine kinase activator activity / potassium ion transport / regulation of cytokinesis / positive regulation of peptidyl-threonine phosphorylation / spindle microtubule / sensory perception of sound / response to calcium ion / positive regulation of protein serine/threonine kinase activity / G2/M transition of mitotic cell cycle / spindle pole / calcium-dependent protein binding / serine-type endopeptidase inhibitor activity / myelin sheath / vesicle / transmembrane transporter binding / G protein-coupled receptor signaling pathway / centrosome / calcium ion binding / protein kinase binding / protein-containing complex / extracellular space / nucleus / metal ion binding / plasma membrane / cytoplasm Similarity search - Function | ||||||
Biological species | Aequorea victoria (jellyfish) Homo sapiens (human) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.5 Å | ||||||
Authors | Shen, H. / Li, T. / Yue, Z. | ||||||
Citation | Journal: Mol Cell / Year: 2021 Title: Structural Basis for the Modulation of Human KCNQ4 by Small-Molecule Drugs. Authors: Tian Li / Kun Wu / Zhenlei Yue / Yifei Wang / Fan Zhang / Huaizong Shen / Abstract: Among the five KCNQ channels, also known as the K7 voltage-gated potassium (K) channels, KCNQ2-KCNQ5 control neuronal excitability. Dysfunctions of KCNQ2-KCNQ5 are associated with neurological ...Among the five KCNQ channels, also known as the K7 voltage-gated potassium (K) channels, KCNQ2-KCNQ5 control neuronal excitability. Dysfunctions of KCNQ2-KCNQ5 are associated with neurological disorders such as epilepsy, deafness, and neuropathic pain. Here, we report the cryoelectron microscopy (cryo-EM) structures of human KCNQ4 and its complexes with the opener retigabine or the blocker linopirdine at overall resolutions of 2.5, 3.1, and 3.3 Å, respectively. In all structures, a phosphatidylinositol 4,5-bisphosphate (PIP) molecule inserts its head group into a cavity within each voltage-sensing domain (VSD), revealing an unobserved binding mode for PIP. Retigabine nestles in each fenestration, inducing local shifts. Instead of staying within the central pore, linopirdine resides in a cytosolic cavity underneath the inner gate. Electrophysiological analyses of various mutants corroborated the structural observations. Our studies reveal the molecular basis for the modulatory mechanism of neuronal KCNQ channels and provide a framework for structure-facilitated drug discovery targeting these important channels. | ||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 7byl.cif.gz | 428.9 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7byl.ent.gz | 321.5 KB | Display | PDB format |
PDBx/mmJSON format | 7byl.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7byl_validation.pdf.gz | 1.1 MB | Display | wwPDB validaton report |
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Full document | 7byl_full_validation.pdf.gz | 1.2 MB | Display | |
Data in XML | 7byl_validation.xml.gz | 61.9 KB | Display | |
Data in CIF | 7byl_validation.cif.gz | 83.6 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/by/7byl ftp://data.pdbj.org/pub/pdb/validation_reports/by/7byl | HTTPS FTP |
-Related structure data
Related structure data | 30244MC 7bymC 7bynC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
#1: Protein | Mass: 109327.836 Da / Num. of mol.: 4 / Mutation: F64L/S65T/K107T/A206K Source method: isolated from a genetically manipulated source Source: (gene. exp.) Aequorea victoria (jellyfish), (gene. exp.) Homo sapiens (human) Gene: GFP, KCNQ4 / Production host: Homo sapiens (human) / References: UniProt: P42212, UniProt: P56696 #2: Protein | Mass: 16852.545 Da / Num. of mol.: 4 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: CALM3, CALML2, CAM3, CAMC, CAMIII / Production host: Homo sapiens (human) / References: UniProt: P0DP25 #3: Chemical | ChemComp-PT5 / [( #4: Chemical | ChemComp-K / #5: Water | ChemComp-HOH / | 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 |
-Sample preparation
Component | Name: Complex of human KCNQ4 and Calmodulin / Type: COMPLEX / Entity ID: #1-#2 / Source: RECOMBINANT |
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Source (natural) | Organism: Homo sapiens (human) |
Source (recombinant) | Organism: Homo sapiens (human) |
Buffer solution | pH: 8 |
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 |
Image recording | Electron dose: 50 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
-Processing
Software | Name: PHENIX / Version: 1.17.1_3660: / Classification: refinement | ||||||||||||||||||||||||
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CTF correction | Type: NONE | ||||||||||||||||||||||||
3D reconstruction | Resolution: 2.5 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 192507 / Symmetry type: POINT | ||||||||||||||||||||||||
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