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Yorodumi- PDB-6cnn: Cryo-EM structure of the human SK4/calmodulin channel complex in ... -
+Open data
-Basic information
Entry | Database: PDB / ID: 6cnn | |||||||||
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Title | Cryo-EM structure of the human SK4/calmodulin channel complex in the Ca2+ bound state I | |||||||||
Components |
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Keywords | MEMBRANE PROTEIN / ion channel / neuroscience / calmodulin | |||||||||
Function / homology | Function and homology information intermediate conductance calcium-activated potassium channel activity / small conductance calcium-activated potassium channel activity / saliva secretion / Ca2+ activated K+ channels / calcium-activated potassium channel activity / stabilization of membrane potential / positive regulation of potassium ion transmembrane transport / cell volume homeostasis / CaM pathway / Cam-PDE 1 activation ...intermediate conductance calcium-activated potassium channel activity / small conductance calcium-activated potassium channel activity / saliva secretion / Ca2+ activated K+ channels / calcium-activated potassium channel activity / stabilization of membrane potential / positive regulation of potassium ion transmembrane transport / cell volume homeostasis / CaM pathway / Cam-PDE 1 activation / Sodium/Calcium exchangers / phospholipid translocation / 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 / 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 / CLEC7A (Dectin-1) induces NFAT activation / mitochondrion-endoplasmic reticulum membrane tethering / autophagosome membrane docking / regulation of cardiac muscle cell action potential / Activation of RAC1 downstream of NMDARs / immune system process / positive regulation of T cell 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 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 / protein phosphatase activator activity / potassium channel activity / RHO GTPases activate PAKs / positive regulation of phosphoprotein phosphatase activity / Ion transport by P-type ATPases / Long-term potentiation / Uptake and function of anthrax toxins / Regulation of MECP2 expression and activity / Calcineurin activates NFAT / 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 / calcium channel inhibitor activity / cellular response to interferon-beta / RHO GTPases activate IQGAPs / regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion / Protein methylation / eNOS activation / Activation of AMPK downstream of NMDARs / regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum / 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 / potassium ion transmembrane transport / sperm midpiece / calcium channel complex / substantia nigra development / adenylate cyclase activator activity / Ras activation upon Ca2+ influx through NMDA receptor / regulation of heart rate / sarcomere / protein serine/threonine kinase activator activity / FCERI mediated Ca+2 mobilization / FCGR3A-mediated IL10 synthesis / VEGFR2 mediated vascular permeability / Antigen activates B Cell Receptor (BCR) leading to generation of second messengers / positive regulation of peptidyl-threonine phosphorylation / VEGFR2 mediated cell proliferation / regulation of cytokinesis / establishment of localization in cell / Translocation of SLC2A4 (GLUT4) to the plasma membrane / positive regulation of protein secretion / spindle microtubule / RAF activation / positive regulation of receptor signaling pathway via JAK-STAT / potassium ion transport / Transcriptional activation of mitochondrial biogenesis / positive regulation of protein serine/threonine kinase activity / Stimuli-sensing channels / defense response / cellular response to type II interferon / spindle pole / response to calcium ion Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.5 Å | |||||||||
Authors | Lee, C.H. / MacKinnon, R. | |||||||||
Funding support | United States, 2items
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Citation | Journal: Science / Year: 2018 Title: Activation mechanism of a human SK-calmodulin channel complex elucidated by cryo-EM structures. Authors: Chia-Hsueh Lee / Roderick MacKinnon / Abstract: Small-conductance Ca-activated K (SK) channels mediate neuron excitability and are associated with synaptic transmission and plasticity. They also regulate immune responses and the size of blood ...Small-conductance Ca-activated K (SK) channels mediate neuron excitability and are associated with synaptic transmission and plasticity. They also regulate immune responses and the size of blood cells. Activation of SK channels requires calmodulin (CaM), but how CaM binds and opens SK channels has been unclear. Here we report cryo-electron microscopy (cryo-EM) structures of a human SK4-CaM channel complex in closed and activated states at 3.4- and 3.5-angstrom resolution, respectively. Four CaM molecules bind to one channel tetramer. Each lobe of CaM serves a distinct function: The C-lobe binds to the channel constitutively, whereas the N-lobe interacts with the S4-S5 linker in a Ca-dependent manner. The S4-S5 linker, which contains two distinct helices, undergoes conformational changes upon CaM binding to open the channel pore. These structures reveal the gating mechanism of SK channels and provide a basis for understanding SK channel pharmacology. | |||||||||
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 | 6cnn.cif.gz | 362.5 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6cnn.ent.gz | 290.2 KB | Display | PDB format |
PDBx/mmJSON format | 6cnn.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 6cnn_validation.pdf.gz | 1.4 MB | Display | wwPDB validaton report |
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Full document | 6cnn_full_validation.pdf.gz | 1.4 MB | Display | |
Data in XML | 6cnn_validation.xml.gz | 56.5 KB | Display | |
Data in CIF | 6cnn_validation.cif.gz | 76.9 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/cn/6cnn ftp://data.pdbj.org/pub/pdb/validation_reports/cn/6cnn | HTTPS FTP |
-Related structure data
Related structure data | 7538MC 7537C 7539C 6cnmC 6cnoC 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
-Protein , 2 types, 8 molecules ABCDEFGH
#1: Protein | Mass: 47758.496 Da / Num. of mol.: 4 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: KCNN4, IK1, IKCA1, KCA4, SK4 / Production host: Homo sapiens (human) / References: UniProt: O15554 #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: CALM1, CALM, CAM, CAM1 / Production host: Homo sapiens (human) / References: UniProt: P0DP23 |
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-Sugars , 1 types, 8 molecules
#5: Sugar | ChemComp-LMT / |
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-Non-polymers , 3 types, 20 molecules
#3: Chemical | ChemComp-K / #4: Chemical | ChemComp-POV / ( #6: Chemical | ChemComp-CA / |
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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: human SK4/calmodulin channel complex / 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: 75 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
-Processing
Software | Name: PHENIX / Version: 1.12_2829: / Classification: refinement | ||||||||||||||||||||||||
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
Symmetry | Point symmetry: C4 (4 fold cyclic) | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.5 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 91511 / Symmetry type: POINT | ||||||||||||||||||||||||
Refinement | Highest resolution: 3.5 Å | ||||||||||||||||||||||||
Refine LS restraints |
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