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Open data
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Basic information
Entry | Database: PDB / ID: 5vms | |||||||||
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Title | CryoEM structure of Xenopus KCNQ1 channel | |||||||||
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![]() | TRANSPORT PROTEIN / CALCIUM BINDING PROTEIN / KCNQ1-CaM complex / potassium channel / Long QT syndrome | |||||||||
Function / homology | ![]() regulation of gastric acid secretion / membrane repolarization / : / establishment of protein localization to mitochondrial membrane / type 3 metabotropic glutamate receptor binding / delayed rectifier potassium channel activity / outward rectifier potassium channel activity / CaM pathway / intestinal absorption / Cam-PDE 1 activation ...regulation of gastric acid secretion / membrane repolarization / : / establishment of protein localization to mitochondrial membrane / type 3 metabotropic glutamate receptor binding / delayed rectifier potassium channel activity / outward rectifier potassium channel activity / CaM pathway / intestinal absorption / Cam-PDE 1 activation / Sodium/Calcium exchangers / regulation of synaptic vesicle endocytosis / Calmodulin induced events / Reduction of cytosolic Ca++ levels / CREB1 phosphorylation through the activation of CaMKII/CaMKK/CaMKIV cascasde / Activation of Ca-permeable Kainate Receptor / Loss of phosphorylation of MECP2 at T308 / monoatomic ion channel complex / CREB1 phosphorylation through the activation of Adenylate Cyclase / PKA activation / negative regulation of high voltage-gated calcium channel activity / CaMK IV-mediated phosphorylation of CREB / Glycogen breakdown (glycogenolysis) / positive regulation of cyclic-nucleotide phosphodiesterase activity / organelle localization by membrane tethering / negative regulation of calcium ion export across plasma membrane / regulation of synaptic vesicle exocytosis / CLEC7A (Dectin-1) induces NFAT activation / regulation of cardiac muscle cell action potential / mitochondrion-endoplasmic reticulum membrane tethering / autophagosome membrane docking / Activation of RAC1 downstream of NMDARs / response to corticosterone / renal absorption / nitric-oxide synthase binding / positive regulation of ryanodine-sensitive calcium-release channel activity / regulation of cell communication by electrical coupling involved in cardiac conduction / Negative regulation of NMDA receptor-mediated neuronal transmission / negative regulation of peptidyl-threonine phosphorylation / Synthesis of IP3 and IP4 in the cytosol / Unblocking of NMDA receptors, glutamate binding and activation / Phase 0 - rapid depolarisation / voltage-gated potassium channel activity / protein phosphatase activator activity / RHO GTPases activate PAKs / positive regulation of phosphoprotein phosphatase activity / Ion transport by P-type ATPases / inner ear development / Long-term potentiation / Uptake and function of anthrax toxins / Calcineurin activates NFAT / Regulation of MECP2 expression and activity / adenylate cyclase binding / catalytic complex / DARPP-32 events / detection of calcium ion / regulation of cardiac muscle contraction / negative regulation of ryanodine-sensitive calcium-release channel activity / Smooth Muscle Contraction / RHO GTPases activate IQGAPs / calcium channel inhibitor activity / cellular response to interferon-beta / positive regulation of DNA binding / regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion / Protein methylation / phosphatidylinositol 3-kinase binding / eNOS activation / Activation of AMPK downstream of NMDARs / regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum / enzyme regulator activity / Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation / positive regulation of protein dephosphorylation / Ion homeostasis / regulation of calcium-mediated signaling / regulation of ryanodine-sensitive calcium-release channel activity / titin binding / positive regulation of protein autophosphorylation / voltage-gated potassium channel complex / sperm midpiece / calcium channel complex / response to amphetamine / activation of adenylate cyclase activity / substantia nigra development / phosphatidylinositol-4,5-bisphosphate binding / adenylate cyclase activator activity / Ras activation upon Ca2+ influx through NMDA receptor / nitric-oxide synthase regulator activity / regulation of heart rate / sarcomere / protein serine/threonine kinase activator activity / FCERI mediated Ca+2 mobilization / FCGR3A-mediated IL10 synthesis / VEGFR2 mediated vascular permeability / positive regulation of peptidyl-threonine phosphorylation / regulation of cytokinesis / Antigen activates B Cell Receptor (BCR) leading to generation of second messengers / VEGFR2 mediated cell proliferation / positive regulation of nitric-oxide synthase activity / Translocation of SLC2A4 (GLUT4) to the plasma membrane / mitochondrial membrane Similarity search - Function | |||||||||
Biological species | ![]() ![]() | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.7 Å | |||||||||
![]() | Mackinnon, R. / Sun, J. | |||||||||
Funding support | ![]()
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![]() | ![]() Title: Cryo-EM Structure of a KCNQ1/CaM Complex Reveals Insights into Congenital Long QT Syndrome. Authors: Ji Sun / Roderick MacKinnon / ![]() Abstract: KCNQ1 is the pore-forming subunit of cardiac slow-delayed rectifier potassium (I) channels. Mutations in the kcnq1 gene are the leading cause of congenital long QT syndrome (LQTS). Here, we present ...KCNQ1 is the pore-forming subunit of cardiac slow-delayed rectifier potassium (I) channels. Mutations in the kcnq1 gene are the leading cause of congenital long QT syndrome (LQTS). Here, we present the cryoelectron microscopy (cryo-EM) structure of a KCNQ1/calmodulin (CaM) complex. The conformation corresponds to an "uncoupled," PIP-free state of KCNQ1, with activated voltage sensors and a closed pore. Unique structural features within the S4-S5 linker permit uncoupling of the voltage sensor from the pore in the absence of PIP. CaM contacts the KCNQ1 voltage sensor through a specific interface involving a residue on CaM that is mutated in a form of inherited LQTS. Using an electrophysiological assay, we find that this mutation on CaM shifts the KCNQ1 voltage-activation curve. This study describes one physiological form of KCNQ1, depolarized voltage sensors with a closed pore in the absence of PIP, and reveals a regulatory interaction between CaM and KCNQ1 that may explain CaM-mediated LQTS. | |||||||||
History |
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Remark 650 | HELIX DETERMINATION METHOD: AUTHOR PROVIDED. |
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Structure visualization
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Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 113.2 KB | Display | ![]() |
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PDB format | ![]() | 80.7 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 741 KB | Display | ![]() |
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Full document | ![]() | 742.6 KB | Display | |
Data in XML | ![]() | 18.8 KB | Display | |
Data in CIF | ![]() | 26.9 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8712MC M: map data used to model this data C: citing same article ( |
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Similar structure data |
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Links
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Assembly
Deposited unit | ![]()
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Symmetry | Point symmetry: (Schoenflies symbol: C4 (4 fold cyclic)) |
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Components
#1: Protein | Mass: 62663.398 Da / Num. of mol.: 1 / Fragment: UNP residues 67-610 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
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#2: Protein | Mass: 16852.545 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() Gene: CALM1, CALM, CAM, CAM1, CALM2, CAM2, CAMB, CALM3, CALML2, CAM3, CAMC, CAMIII Production host: ![]() |
#3: Chemical |
-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: Complex of Xenopus KCNQ1 and CaM / Type: COMPLEX / Entity ID: #1-#2 / Source: RECOMBINANT |
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Molecular weight | Value: 0.3 MDa / Experimental value: NO |
Source (natural) | Organism: ![]() |
Source (recombinant) | Organism: ![]() |
Buffer solution | pH: 7.2 |
Specimen | Conc.: 5 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Chamber temperature: 298 K / Details: 90-100% humidity |
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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 |
Image recording | Electron dose: 1.78 e/Å2 / Detector mode: SUPER-RESOLUTION / Film or detector model: DIRECT ELECTRON DE-64 (8k x 8k) |
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Processing
Software | Name: REFMAC / Version: 5.8.0088 / Classification: refinement | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Symmetry | Point symmetry: C4 (4 fold cyclic) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 3.7 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 69415 Details: Entry was refined using space group P4 and cell parameters a=b=c=332.8 and alpha=beta=gamma=90. Symmetry type: POINT | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement | Resolution: 3.7→122.3 Å / Cor.coef. Fo:Fc: 0.91 / SU B: 40.602 / SU ML: 0.52 Stereochemistry target values: MAXIMUM LIKELIHOOD WITH PHASES Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
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Solvent computation | Ion probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 203.149 Å2
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Refine LS restraints |
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