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Yorodumi- EMDB-51160: Structure of the human two pore domain potassium ion channel TASK... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-51160 | ||||||||||||
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Title | Structure of the human two pore domain potassium ion channel TASK-1 (K2P3.1) | ||||||||||||
Map data | B factor sharpened map | ||||||||||||
Sample |
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Keywords | K2P / membrane protein / potassium channel / ion channel | ||||||||||||
Function / homology | Function and homology information open rectifier potassium channel activity / TWIK-releated acid-sensitive K+ channel (TASK) / Phase 4 - resting membrane potential / stabilization of membrane potential / potassium ion leak channel activity / regulation of resting membrane potential / outward rectifier potassium channel activity / S100 protein binding / cellular response to zinc ion / negative regulation of cytosolic calcium ion concentration ...open rectifier potassium channel activity / TWIK-releated acid-sensitive K+ channel (TASK) / Phase 4 - resting membrane potential / stabilization of membrane potential / potassium ion leak channel activity / regulation of resting membrane potential / outward rectifier potassium channel activity / S100 protein binding / cellular response to zinc ion / negative regulation of cytosolic calcium ion concentration / cochlea development / monoatomic ion channel activity / potassium channel activity / potassium ion transmembrane transport / potassium ion transport / monoatomic ion transmembrane transport / chemical synaptic transmission / cellular response to hypoxia / response to xenobiotic stimulus / synapse / plasma membrane Similarity search - Function | ||||||||||||
Biological species | Homo sapiens (human) | ||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.13 Å | ||||||||||||
Authors | Rodstrom KEJ / Hall PH / Tucker SJ | ||||||||||||
Funding support | United Kingdom, 3 items
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Citation | Journal: Structure / Year: 2024 Title: Structures of TASK-1 and TASK-3 K2P channels provide insight into their gating and dysfunction in disease. Authors: Peter Rory Hall / Thibault Jouen-Tachoire / Marcus Schewe / Peter Proks / Thomas Baukrowitz / Elisabeth P Carpenter / Simon Newstead / Karin E J Rödström / Stephen J Tucker / Abstract: TASK-1 and TASK-3 are pH-sensitive two-pore domain (K2P/KCNK) K channels. Their functional roles make them promising targets for treatment of multiple disorders including sleep apnea, pain, and ...TASK-1 and TASK-3 are pH-sensitive two-pore domain (K2P/KCNK) K channels. Their functional roles make them promising targets for treatment of multiple disorders including sleep apnea, pain, and atrial fibrillation. Mutations in these channels are also associated with neurodevelopmental and hypertensive disorders. A previous crystal structure of TASK-1 revealed a lower "X-gate" as a hotspot for missense gain-of-function (GoF) mutations associated with DDSA (developmental delay with sleep apnea). However, the mechanisms of gating in TASK channels are still not fully understood. Here, we resolve structures for both human TASK-1 and TASK-3 by cryoelectron microscopy (cryo-EM), as well as a recurrent TASK-3 variant (G236R) associated with KCNK9 imprinting syndrome (KIS) (formerly known as Birk-Barel syndrome). Combined with functional studies of the X-gating mechanism, we provide evidence for how a highly conserved gating mechanism becomes defective in disease, and also provide further insight into the pathway of conformational changes that underlie the pH-dependent inhibition of TASK channel activity. | ||||||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_51160.map.gz | 32.8 MB | EMDB map data format | |
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Header (meta data) | emd-51160-v30.xml emd-51160.xml | 18.6 KB 18.6 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_51160_fsc.xml | 8.4 KB | Display | FSC data file |
Images | emd_51160.png | 126.2 KB | ||
Masks | emd_51160_msk_1.map emd_51160_msk_2.map | 64 MB 64 MB | Mask map | |
Filedesc metadata | emd-51160.cif.gz | 6.4 KB | ||
Others | emd_51160_half_map_1.map.gz emd_51160_half_map_2.map.gz | 59.2 MB 59.2 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-51160 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-51160 | HTTPS FTP |
-Validation report
Summary document | emd_51160_validation.pdf.gz | 830.5 KB | Display | EMDB validaton report |
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Full document | emd_51160_full_validation.pdf.gz | 830.1 KB | Display | |
Data in XML | emd_51160_validation.xml.gz | 16.4 KB | Display | |
Data in CIF | emd_51160_validation.cif.gz | 21.2 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-51160 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-51160 | HTTPS FTP |
-Related structure data
Related structure data | 9g9xMC 9g9vC 9g9wC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_51160.map.gz / Format: CCP4 / Size: 64 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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Annotation | B factor sharpened map | ||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 0.832 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Mask #1
File | emd_51160_msk_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Mask #2
File | emd_51160_msk_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: Half map A
File | emd_51160_half_map_1.map | ||||||||||||
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Annotation | Half map A | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Half map B
File | emd_51160_half_map_2.map | ||||||||||||
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Annotation | Half map B | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
-Entire : K2P3.1 homodimer
Entire | Name: K2P3.1 homodimer |
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Components |
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-Supramolecule #1: K2P3.1 homodimer
Supramolecule | Name: K2P3.1 homodimer / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1 Details: Protein generated by removal of the 10xHis and FLAG purification tags with TEV protease cleavage |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 600 KDa |
-Macromolecule #1: Potassium channel subfamily K member 3
Macromolecule | Name: Potassium channel subfamily K member 3 / type: protein_or_peptide / ID: 1 Details: K2P3.1 residues M1 to E259 with a TEV protease site. Fused purification tags were cleaved prior to EM sample preparation. Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 30.117014 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
Sequence | String: MKRQNVRTLA LIVCTFTYLL VGAAVFDALE SEPELIERQR LELRQQELRA RYNLSQGGYE ELERVVLRLK PHKAGVQWRF AGSFYFAIT VITTIGYGHA APSTDGGKVF CMFYALLGIP LTLVMFQSLG ERINTLVRYL LHRAKKGLGM RRADVSMANM V LIGFFSCI ...String: MKRQNVRTLA LIVCTFTYLL VGAAVFDALE SEPELIERQR LELRQQELRA RYNLSQGGYE ELERVVLRLK PHKAGVQWRF AGSFYFAIT VITTIGYGHA APSTDGGKVF CMFYALLGIP LTLVMFQSLG ERINTLVRYL LHRAKKGLGM RRADVSMANM V LIGFFSCI STLCIGAAAF SHYEHWTFFQ AYYYCFITLT TIGFGDYVAL QKDQALQTQP QYVAFSFVYI LTGLTVIGAF LN LVVLRFM TMNAEDEKRD AENLYFQ UniProtKB: Potassium channel subfamily K member 3 |
-Macromolecule #2: CHOLESTEROL HEMISUCCINATE
Macromolecule | Name: CHOLESTEROL HEMISUCCINATE / type: ligand / ID: 2 / Number of copies: 4 / Formula: Y01 |
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Molecular weight | Theoretical: 486.726 Da |
Chemical component information | ChemComp-Y01: |
-Macromolecule #3: POTASSIUM ION
Macromolecule | Name: POTASSIUM ION / type: ligand / ID: 3 / Number of copies: 3 / Formula: K |
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Molecular weight | Theoretical: 39.098 Da |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 3.6 mg/mL |
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Buffer | pH: 7.5 Details: 20 mM HEPES pH 7.5, 200 mM KCl, 0.045% w/v UDM, 0.0045% w/v CHS |
Grid | Model: Quantifoil R1.2/1.3 / Material: COPPER / Mesh: 300 / Support film - Material: CARBON / Support film - topology: HOLEY / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Time: 120 sec. |
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277 K / Instrument: FEI VITROBOT MARK IV / Details: Grid blotted for 3.5 seconds. |
Details | Monodisperse sample |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Specialist optics | Energy filter - Name: GIF Bioquantum / Energy filter - Slit width: 20 eV |
Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Number grids imaged: 1 / Number real images: 17288 / Average electron dose: 41.17 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.5 µm / Nominal defocus min: 1.25 µm / Nominal magnification: 105000 |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |