+Open data
-Basic information
Entry | Database: PDB / ID: 8sik | ||||||
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Title | KCNQ1 with voltage sensor in the up conformation | ||||||
Components |
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Keywords | MEMBRANE PROTEIN / voltage-gated potassium channel | ||||||
Function / homology | Function and homology information 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 / membrane repolarization during ventricular cardiac muscle cell action potential / regulation of atrial cardiac muscle cell membrane repolarization / iodide transport / Phase 2 - plateau phase / potassium ion export across plasma membrane / membrane repolarization during cardiac muscle cell action potential / 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 / auditory receptor cell development / detection of mechanical stimulus involved in sensory perception of sound / regulation of membrane repolarization / protein phosphatase 1 binding / delayed rectifier potassium channel activity / positive regulation of potassium ion transmembrane transport / Voltage gated Potassium channels / outward rectifier potassium channel activity / potassium ion homeostasis / ventricular cardiac muscle cell action potential / non-motile cilium assembly / regulation of ventricular cardiac muscle cell membrane repolarization / CaM pathway / Cam-PDE 1 activation / intestinal absorption / Sodium/Calcium exchangers / regulation of heart contraction / Calmodulin induced events / Reduction of cytosolic Ca++ levels / Activation of Ca-permeable Kainate Receptor / CREB1 phosphorylation through the activation of CaMKII/CaMKK/CaMKIV cascasde / Loss of phosphorylation of MECP2 at T308 / CREB1 phosphorylation through the activation of Adenylate Cyclase / PKA activation / negative regulation of high voltage-gated calcium channel activity / ciliary base / monoatomic ion channel complex / inner ear morphogenesis / CaMK IV-mediated phosphorylation of CREB / Glycogen breakdown (glycogenolysis) / negative regulation of calcium ion export across plasma membrane / positive regulation of heart rate / organelle localization by membrane tethering / Activation of RAC1 downstream of NMDARs / regulation of cardiac muscle cell action potential / mitochondrion-endoplasmic reticulum membrane tethering / CLEC7A (Dectin-1) induces NFAT activation / autophagosome membrane docking / cochlea development / renal absorption / adrenergic receptor signaling pathway / positive regulation of ryanodine-sensitive calcium-release channel activity / potassium ion import across plasma membrane / Negative regulation of NMDA receptor-mediated neuronal transmission / regulation of cell communication by electrical coupling involved in cardiac conduction / Unblocking of NMDA receptors, glutamate binding and activation / negative regulation of peptidyl-threonine phosphorylation / Synthesis of IP3 and IP4 in the cytosol / regulation of heart rate by cardiac conduction / Phase 0 - rapid depolarisation / protein kinase A regulatory subunit binding / protein phosphatase activator activity / RHO GTPases activate PAKs / voltage-gated potassium channel activity / protein kinase A catalytic subunit binding / inner ear development / social behavior / positive regulation of cyclic-nucleotide phosphodiesterase activity / positive regulation of phosphoprotein phosphatase activity / Long-term potentiation / Ion transport by P-type ATPases / Uptake and function of anthrax toxins / Calcineurin activates NFAT / Regulation of MECP2 expression and activity / catalytic complex / DARPP-32 events / detection of calcium ion / negative regulation of ryanodine-sensitive calcium-release channel activity / Smooth Muscle Contraction / RHO GTPases activate IQGAPs / regulation of cardiac muscle contraction / calcium channel inhibitor activity / cellular response to interferon-beta / regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion / Protein methylation / voltage-gated potassium channel complex Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.9 Å | ||||||
Authors | Mandala, V.S. / MacKinnon, R. | ||||||
Funding support | United States, 1items
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Citation | Journal: Proc Natl Acad Sci U S A / Year: 2023 Title: The membrane electric field regulates the PIP-binding site to gate the KCNQ1 channel. Authors: Venkata Shiva Mandala / Roderick MacKinnon / Abstract: Voltage-dependent ion channels underlie the propagation of action potentials and other forms of electrical activity in cells. In these proteins, voltage sensor domains (VSDs) regulate opening and ...Voltage-dependent ion channels underlie the propagation of action potentials and other forms of electrical activity in cells. In these proteins, voltage sensor domains (VSDs) regulate opening and closing of the pore through the displacement of their positive-charged S4 helix in response to the membrane voltage. The movement of S4 at hyperpolarizing membrane voltages in some channels is thought to directly clamp the pore shut through the S4-S5 linker helix. The KCNQ1 channel (also known as K7.1), which is important for heart rhythm, is regulated not only by membrane voltage but also by the signaling lipid phosphatidylinositol 4,5-bisphosphate (PIP). KCNQ1 requires PIP to open and to couple the movement of S4 in the VSD to the pore. To understand the mechanism of this voltage regulation, we use cryogenic electron microscopy to visualize the movement of S4 in the human KCNQ1 channel in lipid membrane vesicles with a voltage difference across the membrane, i.e., an applied electric field in the membrane. Hyperpolarizing voltages displace S4 in such a manner as to sterically occlude the PIP-binding site. Thus, in KCNQ1, the voltage sensor acts primarily as a regulator of PIP binding. The voltage sensors' influence on the channel's gate is indirect through the reaction sequence: voltage sensor movement → alter PIP ligand affinity → alter pore opening. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8sik.cif.gz | 395.7 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8sik.ent.gz | 320.3 KB | Display | PDB format |
PDBx/mmJSON format | 8sik.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/si/8sik ftp://data.pdbj.org/pub/pdb/validation_reports/si/8sik | HTTPS FTP |
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-Related structure data
Related structure data | 40508MC 8simC 8sinC M: map data used to model this data C: citing same article (ref.) |
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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
#1: Protein | Mass: 16852.545 Da / Num. of mol.: 4 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: CALM1, CALM, CAM, CAM1 / Production host: Homo sapiens (human) / References: UniProt: P0DP23 #2: Protein | Mass: 63258.574 Da / Num. of mol.: 4 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: KCNQ1, KCNA8, KCNA9, KVLQT1 / Production host: Homo sapiens (human) / References: UniProt: P51787 #3: Chemical | ChemComp-CA / 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: Complex of KCNQ1 (Kv7.1) channel bound to calmodulin-Ca2+ Type: COMPLEX / Entity ID: #1-#2 / Source: RECOMBINANT |
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Molecular weight | Experimental value: NO |
Source (natural) | Organism: Homo sapiens (human) |
Source (recombinant) | Organism: Homo sapiens (human) |
Buffer solution | pH: 8 |
Specimen | Conc.: 0.2 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 293 K |
-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: 2000 nm / Nominal defocus min: 1000 nm |
Image recording | Electron dose: 60 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) |
-Processing
Software | Name: PHENIX / Version: 1.20.1_4487: / Classification: refinement | ||||||||||||||||||||||||
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
Symmetry | Point symmetry: C4 (4 fold cyclic) | ||||||||||||||||||||||||
3D reconstruction | Resolution: 2.9 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 200862 / Symmetry type: POINT | ||||||||||||||||||||||||
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