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Open data
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Basic information
Entry | Database: PDB / ID: 7xnn | |||||||||||||||||||||
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Title | human KCNQ1-CaM-ML277-PIP2 complex in state B | |||||||||||||||||||||
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![]() | MEMBRANE PROTEIN / potassium voltage-gated channel / ML277 / PIP2 | |||||||||||||||||||||
Function / homology | ![]() gastrin-induced gastric acid secretion / corticosterone secretion / voltage-gated potassium channel activity involved in atrial cardiac muscle cell action potential repolarization / basolateral part of cell / lumenal side of membrane / negative regulation of voltage-gated potassium channel activity / rhythmic behavior / regulation of gastric acid secretion / stomach development / membrane repolarization during atrial cardiac muscle cell action potential ...gastrin-induced gastric acid secretion / corticosterone secretion / voltage-gated potassium channel activity involved in atrial cardiac muscle cell action potential repolarization / basolateral part of cell / lumenal side of membrane / negative regulation of voltage-gated potassium channel activity / rhythmic behavior / regulation of gastric acid secretion / stomach development / membrane repolarization during atrial cardiac muscle cell action potential / Phase 3 - rapid repolarisation / voltage-gated potassium channel activity involved in cardiac muscle cell action potential repolarization / membrane repolarization during action potential / iodide transport / membrane repolarization during ventricular cardiac muscle cell action potential / regulation of atrial cardiac muscle cell membrane repolarization / Phase 2 - plateau phase / membrane repolarization during cardiac muscle cell action potential / potassium ion export across plasma membrane / intracellular chloride ion homeostasis / renal sodium ion absorption / negative regulation of delayed rectifier potassium channel activity / voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization / atrial cardiac muscle cell action potential / detection of mechanical stimulus involved in sensory perception of sound / auditory receptor cell development / regulation of membrane repolarization / protein phosphatase 1 binding / positive regulation of potassium ion transmembrane transport / Voltage gated Potassium channels / potassium ion homeostasis / ventricular cardiac muscle cell action potential / non-motile cilium assembly / delayed rectifier potassium channel activity / regulation of ventricular cardiac muscle cell membrane repolarization / outward rectifier potassium channel activity / intestinal absorption / monoatomic ion channel complex / negative regulation of high voltage-gated calcium channel activity / ciliary base / positive regulation of cyclic-nucleotide phosphodiesterase activity / regulation of heart contraction / negative regulation of calcium ion export across plasma membrane / inner ear morphogenesis / regulation of cardiac muscle cell action potential / positive regulation of heart rate / renal absorption / cochlea development / adrenergic receptor signaling pathway / 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 / protein kinase A regulatory subunit binding / protein phosphatase activator activity / regulation of heart rate by cardiac conduction / potassium ion import across plasma membrane / protein kinase A catalytic subunit binding / positive regulation of phosphoprotein phosphatase activity / social behavior / inner ear development / adenylate cyclase binding / catalytic complex / detection of calcium ion / regulation of cardiac muscle contraction / 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 / cardiac muscle contraction / cellular response to cAMP / positive regulation of protein dephosphorylation / regulation of calcium-mediated signaling / potassium ion transmembrane transport / titin binding / voltage-gated potassium channel complex / transport vesicle / positive regulation of protein autophosphorylation / positive regulation of cardiac muscle contraction / sperm midpiece / cellular response to epinephrine stimulus / calcium channel complex / substantia nigra development / phosphatidylinositol-4,5-bisphosphate binding / adenylate cyclase activator activity / regulation of heart rate / sarcomere / protein serine/threonine kinase activator activity / erythrocyte differentiation / positive regulation of peptidyl-threonine phosphorylation / regulation of cytokinesis / sensory perception of sound / response to insulin / cytoplasmic vesicle membrane / positive regulation of protein serine/threonine kinase activity / spindle microtubule / regulation of blood pressure / spindle pole / response to calcium ion / G2/M transition of mitotic cell cycle / glucose metabolic process Similarity search - Function | |||||||||||||||||||||
Biological species | ![]() | |||||||||||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.5 Å | |||||||||||||||||||||
![]() | Ma, D. / Guo, J. | |||||||||||||||||||||
Funding support | ![]()
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![]() | ![]() Title: Structural mechanisms for the activation of human cardiac KCNQ1 channel by electro-mechanical coupling enhancers. Authors: Demin Ma / Ling Zhong / Zhenzhen Yan / Jing Yao / Yan Zhang / Fan Ye / Yuan Huang / Dongwu Lai / Wei Yang / Panpan Hou / Jiangtao Guo / ![]() Abstract: The cardiac KCNQ1 potassium channel carries the important current and controls the heart rhythm. Hundreds of mutations in KCNQ1 can cause life-threatening cardiac arrhythmia. Although KCNQ1 ...The cardiac KCNQ1 potassium channel carries the important current and controls the heart rhythm. Hundreds of mutations in KCNQ1 can cause life-threatening cardiac arrhythmia. Although KCNQ1 structures have been recently resolved, the structural basis for the dynamic electro-mechanical coupling, also known as the voltage sensor domain-pore domain (VSD-PD) coupling, remains largely unknown. In this study, utilizing two VSD-PD coupling enhancers, namely, the membrane lipid phosphatidylinositol 4,5-bisphosphate (PIP) and a small-molecule ML277, we determined 2.5-3.5 Å resolution cryo-electron microscopy structures of full-length human KCNQ1-calmodulin (CaM) complex in the apo closed, ML277-bound open, and ML277-PIP-bound open states. ML277 binds at the "elbow" pocket above the S4-S5 linker and directly induces an upward movement of the S4-S5 linker and the opening of the activation gate without affecting the C-terminal domain (CTD) of KCNQ1. PIP binds at the cleft between the VSD and the PD and brings a large structural rearrangement of the CTD together with the CaM to activate the PD. These findings not only elucidate the structural basis for the dynamic VSD-PD coupling process during KCNQ1 gating but also pave the way to develop new therapeutics for anti-arrhythmia. | |||||||||||||||||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 600.2 KB | Display | ![]() |
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PDB format | ![]() | 489.5 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 1.5 MB | Display | ![]() |
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Full document | ![]() | 1.6 MB | Display | |
Data in XML | ![]() | 67 KB | Display | |
Data in CIF | ![]() | 93.6 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 33319MC ![]() 7xniC ![]() 7xnkC ![]() 7xnlC M: map data used to model this data C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
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Assembly
Deposited unit | ![]()
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Components
#1: Protein | Mass: 19615.445 Da / Num. of mol.: 4 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() #2: Protein | Mass: 76487.297 Da / Num. of mol.: 4 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() #3: Chemical | ChemComp-K / #4: Chemical | ChemComp-I0S / ( #5: Chemical | ChemComp-PIO / [( 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 |
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Sample preparation
Component | Name: human KCNQ1-CaM-ML277-PIP2 complex in state B / Type: ORGANELLE OR CELLULAR COMPONENT / Entity ID: #1-#2 / Source: RECOMBINANT |
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Source (natural) | Organism: ![]() |
Source (recombinant) | Organism: ![]() |
Buffer solution | pH: 8 |
Specimen | 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: BRIGHT FIELD / Nominal defocus max: -1300 nm / Nominal defocus min: -1100 nm |
Image recording | Electron dose: 64 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
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Processing
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
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3D reconstruction | Resolution: 2.5 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 257550 / Symmetry type: POINT |