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Open data
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Basic information
Entry | Database: PDB / ID: 7vnq | ||||||
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Title | Structure of human KCNQ4-ML213 complex in nanodisc | ||||||
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![]() | MEMBRANE PROTEIN / KCNQ4 / ML213 / cryo-EM / nanodisc | ||||||
Function / homology | ![]() 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 / positive regulation of cyclic-nucleotide phosphodiesterase activity / negative regulation of calcium ion export across plasma membrane / inner ear morphogenesis / 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 / positive regulation of cyclic-nucleotide phosphodiesterase activity / negative regulation of calcium ion export across plasma membrane / inner ear morphogenesis / 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 / voltage-gated potassium channel activity / potassium channel activity / protein phosphatase activator activity / positive regulation of phosphoprotein phosphatase activity / adenylate cyclase binding / carbohydrate transmembrane transporter activity / catalytic complex / maltose binding / detection of calcium ion / regulation of cardiac muscle contraction / maltose transport / maltodextrin transmembrane transport / negative regulation of ryanodine-sensitive calcium-release channel activity / 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 / ATP-binding cassette (ABC) transporter complex, substrate-binding subunit-containing / regulation of calcium-mediated signaling / positive regulation of protein dephosphorylation / potassium ion transmembrane transport / titin binding / voltage-gated potassium channel complex / positive regulation of protein autophosphorylation / sperm midpiece / calcium channel complex / substantia nigra development / adenylate cyclase activator activity / regulation of heart rate / sarcomere / protein serine/threonine kinase activator activity / basal plasma membrane / positive regulation of peptidyl-threonine phosphorylation / regulation of cytokinesis / sensory perception of sound / potassium ion transport / positive regulation of protein serine/threonine kinase activity / spindle microtubule / spindle pole / response to calcium ion / G2/M transition of mitotic cell cycle / calcium-dependent protein binding / myelin sheath / outer membrane-bounded periplasmic space / vesicle / transmembrane transporter binding / G protein-coupled receptor signaling pathway / centrosome / calcium ion binding / protein kinase binding / protein-containing complex / nucleus / plasma membrane / cytoplasm Similarity search - Function | ||||||
Biological species | ![]() ![]() ![]() | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.96 Å | ||||||
![]() | Xu, F. / Zheng, Y. | ||||||
Funding support | ![]()
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![]() | ![]() Title: Structural insights into the lipid and ligand regulation of a human neuronal KCNQ channel. Authors: You Zheng / Heng Liu / Yuxin Chen / Shaowei Dong / Fang Wang / Shengyi Wang / Geng-Lin Li / Yilai Shu / Fei Xu / ![]() Abstract: The KCNQ family (KCNQ1-KCNQ5) of voltage-gated potassium channels plays critical roles in many physiological and pathological processes. It is known that the channel opening of all KCNQs relies on ...The KCNQ family (KCNQ1-KCNQ5) of voltage-gated potassium channels plays critical roles in many physiological and pathological processes. It is known that the channel opening of all KCNQs relies on the signaling lipid molecule phosphatidylinositol 4,5-bisphosphate (PIP2). However, the molecular mechanism of PIP2 in modulating the opening of the four neuronal KCNQ channels (KCNQ2-KCNQ5), which are essential for regulating neuronal excitability, remains largely elusive. Here, we report the cryoelectron microscopy (cryo-EM) structures of human KCNQ4 determined in complex with the activator ML213 in the absence or presence of PIP2. Two PIP2 molecules are identified in the open-state structure of KCNQ4, which act as a bridge to couple the voltage-sensing domain (VSD) and pore domain (PD) of KCNQ4 leading to the channel opening. Our findings reveal the binding sites and activation mechanisms of ML213 and PIP2 for neuronal KCNQ channels, providing a framework for therapeutic intervention targeting on these important channels. | ||||||
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Structure visualization
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Structure viewer | Molecule: ![]() ![]() |
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PDBx/mmCIF format | ![]() | 414.9 KB | Display | ![]() |
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PDB format | ![]() | 306.2 KB | Display | ![]() |
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-Validation report
Summary document | ![]() | 1.2 MB | Display | ![]() |
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Full document | ![]() | 1.2 MB | Display | |
Data in XML | ![]() | 57.5 KB | Display | |
Data in CIF | ![]() | 83.8 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 32045MC ![]() 7vnpC ![]() 7vnrC M: map data used to model this data C: citing same article ( |
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Similar structure data |
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Assembly
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Components
#1: Protein | Mass: 116541.383 Da / Num. of mol.: 4 Source method: isolated from a genetically manipulated source Details: The fusion protein of Potassium voltage-gated channel subfamily KQT member 4, linker, and Maltodextrin-binding protein Source: (gene. exp.) ![]() ![]() ![]() Gene: KCNQ4, ECBD_4002 / Strain: B / BL21-DE3 / Production host: ![]() #2: Protein | Mass: 16852.545 Da / Num. of mol.: 4 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() #3: Chemical | ChemComp-7YV / ( #4: Chemical | 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 |
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Sample preparation
Component | Name: KCNQ4-ML213 complex in nanodisc / Type: COMPLEX / Entity ID: #1-#2 / Source: RECOMBINANT |
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Source (natural) | Organism: ![]() |
Source (recombinant) | Organism: ![]() |
Buffer solution | pH: 7.4 |
Specimen | Conc.: 2 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
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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: ![]() |
Electron lens | Mode: DARK FIELD |
Image recording | Electron dose: 16.8 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
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Processing
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
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3D reconstruction | Resolution: 2.96 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 69573 / Symmetry type: POINT |