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Yorodumi- PDB-8k1q: Human TWIK-related acid-sensitive potassium channel TASK3 at pH 6... -
+Open data
-Basic information
Entry | Database: PDB / ID: 8k1q | |||||||||||||||
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Title | Human TWIK-related acid-sensitive potassium channel TASK3 at pH 6.0, 5 mM KCl and 135 mM NaCl | |||||||||||||||
Components | Potassium channel subfamily K member 9 | |||||||||||||||
Keywords | MEMBRANE PROTEIN / Acid-sensitive / potassium ion channel / C-type / gating mechanism | |||||||||||||||
Function / homology | Function and homology information TWIK-releated acid-sensitive K+ channel (TASK) / Phase 4 - resting membrane potential / stabilization of membrane potential / potassium ion leak channel activity / outward rectifier potassium channel activity / potassium ion import across plasma membrane / potassium channel activity / potassium ion transmembrane transport / potassium ion transport / synaptic vesicle / plasma membrane Similarity search - Function | |||||||||||||||
Biological species | Homo sapiens (human) | |||||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.68 Å | |||||||||||||||
Authors | Chen, S. / Lin, H. | |||||||||||||||
Funding support | China, 4items
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Citation | Journal: Proc Natl Acad Sci U S A / Year: 2024 Title: C-type inactivation and proton modulation mechanisms of the TASK3 channel. Authors: Huajian Lin / Junnan Li / Qiansen Zhang / Huaiyu Yang / Shanshuang Chen / Abstract: The TWIK-related acid-sensitive K channel 3 (TASK3) belongs to the two-pore domain (K2P) potassium channel family, which regulates cell excitability by mediating a constitutive "leak" potassium ...The TWIK-related acid-sensitive K channel 3 (TASK3) belongs to the two-pore domain (K2P) potassium channel family, which regulates cell excitability by mediating a constitutive "leak" potassium efflux in the nervous system. Extracellular acidification inhibits TASK3 channel, but the molecular mechanism by which channel inactivation is coupled to pH decrease remains unclear. Here, we report the cryo-electron microscopy structures of human TASK3 at neutral and acidic pH. Structural comparison revealed selectivity filter (SF) rearrangements upon acidification, characteristic of C-type inactivation, but with a unique structural basis. The extracellular mouth of the SF was prominently dilated and simultaneously blocked by a hydrophobic gate. His98 protonation shifted the conformational equilibrium between the conductive and C-type inactivated SF toward the latter by engaging a cation-π interaction with Trp78, consistent with molecular dynamics simulations and electrophysiological experiments. Our work illustrated how TASK3 is gated in response to extracellular pH change and implies how physiological stimuli might directly modulate the C-type gating of K2P channels. | |||||||||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8k1q.cif.gz | 101.3 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8k1q.ent.gz | 77 KB | Display | PDB format |
PDBx/mmJSON format | 8k1q.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8k1q_validation.pdf.gz | 597.3 KB | Display | wwPDB validaton report |
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Full document | 8k1q_full_validation.pdf.gz | 603.7 KB | Display | |
Data in XML | 8k1q_validation.xml.gz | 11.1 KB | Display | |
Data in CIF | 8k1q_validation.cif.gz | 15.2 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/k1/8k1q ftp://data.pdbj.org/pub/pdb/validation_reports/k1/8k1q | HTTPS FTP |
-Related structure data
Related structure data | 36799MC 8k1jC 8k1vC 8k1zC 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: 31173.238 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: KCNK9, TASK3 / Production host: eukaryotic plasmids (others) / References: UniProt: Q9NPC2 #2: Chemical | ChemComp-Y01 / #3: Chemical | #4: Water | ChemComp-HOH / | Has ligand of interest | Y | |
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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: CHS / Type: COMPLEX / Entity ID: #1 / Source: RECOMBINANT | ||||||||||||||||||||
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Source (natural) | Organism: Homo sapiens (human) | ||||||||||||||||||||
Source (recombinant) | Organism: eukaryotic plasmids (others) | ||||||||||||||||||||
Buffer solution | pH: 8 | ||||||||||||||||||||
Buffer component |
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Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||||||
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: NITROGEN / Humidity: 100 % / Chamber temperature: 281.15 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 FIELD / Nominal magnification: 81000 X / Nominal defocus max: 2500 nm / Nominal defocus min: 1500 nm |
Image recording | Electron dose: 50 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
-Processing
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
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Symmetry | Point symmetry: C2 (2 fold cyclic) | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.68 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 291294 / Symmetry type: POINT | ||||||||||||||||||||||||
Refine LS restraints |
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