+Open data
-Basic information
Entry | Database: PDB / ID: 7sk0 | |||||||||
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Title | TWIK1 in MSP1D1 lipid nanodisc at pH 7.4 | |||||||||
Components | Potassium channel subfamily K member 1 | |||||||||
Keywords | TRANSPORT PROTEIN / K+ ion Channel / pH | |||||||||
Function / homology | Function and homology information Tandem of pore domain in a weak inwardly rectifying K+ channels (TWIK) / Phase 4 - resting membrane potential / inward rectifier potassium channel complex / voltage-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential / potassium channel complex / stabilization of membrane potential / regulation of resting membrane potential / potassium ion leak channel activity / inward rectifier potassium channel activity / outward rectifier potassium channel activity ...Tandem of pore domain in a weak inwardly rectifying K+ channels (TWIK) / Phase 4 - resting membrane potential / inward rectifier potassium channel complex / voltage-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential / potassium channel complex / stabilization of membrane potential / regulation of resting membrane potential / potassium ion leak channel activity / inward rectifier potassium channel activity / outward rectifier potassium channel activity / sodium channel activity / potassium channel activity / sodium ion transmembrane transport / potassium ion transmembrane transport / synaptic membrane / response to nicotine / brush border membrane / recycling endosome / perikaryon / endosome / apical plasma membrane / dendrite / identical protein binding / membrane / plasma membrane Similarity search - Function | |||||||||
Biological species | Rattus norvegicus (Norway rat) | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.33 Å | |||||||||
Authors | Turney, T.S. / Brohawn, S.G. | |||||||||
Funding support | United States, 2items
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Citation | Journal: Nat Commun / Year: 2022 Title: Structural Basis for pH-gating of the K channel TWIK1 at the selectivity filter. Authors: Toby S Turney / Vivian Li / Stephen G Brohawn / Abstract: TWIK1 (K2P1.1, KCNK1) is a widely expressed pH-gated two-pore domain K channel (K2P) that contributes to cardiac rhythm generation and insulin release from pancreatic beta cells. TWIK1 displays ...TWIK1 (K2P1.1, KCNK1) is a widely expressed pH-gated two-pore domain K channel (K2P) that contributes to cardiac rhythm generation and insulin release from pancreatic beta cells. TWIK1 displays unique properties among K2Ps including low basal activity and inhibition by extracellular protons through incompletely understood mechanisms. Here, we present cryo-EM structures of TWIK1 in lipid nanodiscs at high and low pH that reveal a previously undescribed gating mechanism at the K selectivity filter. At high pH, TWIK1 adopts an open conformation. At low pH, protonation of an extracellular histidine results in a cascade of conformational changes that close the channel by sealing the top of the selectivity filter, displacing the helical cap to block extracellular ion access pathways, and opening gaps for lipid block of the intracellular cavity. These data provide a mechanistic understanding for extracellular pH-gating of TWIK1 and illustrate how diverse mechanisms have evolved to gate the selectivity filter of K channels. #1: Journal: Biorxiv / Year: 2021 Title: Structural Basis for pH-Gating of the K + Channel TWIK1 at the Selectivity Filter Authors: Turney, T.S. / Li, V. / Brohawn, S.G. | |||||||||
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 | 7sk0.cif.gz | 105.4 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7sk0.ent.gz | 78.7 KB | Display | PDB format |
PDBx/mmJSON format | 7sk0.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7sk0_validation.pdf.gz | 826.5 KB | Display | wwPDB validaton report |
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Full document | 7sk0_full_validation.pdf.gz | 829.3 KB | Display | |
Data in XML | 7sk0_validation.xml.gz | 28.1 KB | Display | |
Data in CIF | 7sk0_validation.cif.gz | 38.7 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/sk/7sk0 ftp://data.pdbj.org/pub/pdb/validation_reports/sk/7sk0 | HTTPS FTP |
-Related structure data
Related structure data | 25168MC 7sk1C 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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-Components
#1: Protein | Mass: 38265.984 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Rattus norvegicus (Norway rat) / Gene: Kcnk1 / Production host: Komagataella pastoris (fungus) / References: UniProt: Q9Z2T2 #2: Chemical | #3: Chemical | ChemComp-K / Has ligand of interest | Y | Has protein modification | 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: TWIK1 in MSP1D1 Lipid Nanodisc at pH 7.4 / Type: COMPLEX / Entity ID: #1 / Source: RECOMBINANT | ||||||||||||||||||||
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Source (natural) | Organism: Rattus norvegicus (Norway rat) | ||||||||||||||||||||
Source (recombinant) | Organism: Komagataella pastoris (fungus) | ||||||||||||||||||||
Buffer solution | pH: 7.4 | ||||||||||||||||||||
Buffer component |
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Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||||||
Specimen support | Grid type: Quantifoil R1.2/1.3 | ||||||||||||||||||||
Vitrification | Instrument: FEI VITROBOT MARK III / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 277 K |
-Electron microscopy imaging
Experimental equipment | Model: Talos Arctica / Image courtesy: FEI Company |
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Microscopy | Model: FEI TALOS ARCTICA |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 200 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD |
Image recording | Electron dose: 49.715 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
-Processing
Software | Name: PHENIX / Version: 1.18.2_3874: / Classification: refinement | ||||||||||||||||||||||||||||||||||||
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EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||||||||||
Particle selection | Num. of particles selected: 2872868 | ||||||||||||||||||||||||||||||||||||
Symmetry | Point symmetry: C2 (2 fold cyclic) | ||||||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 3.33 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 92438 / Symmetry type: POINT | ||||||||||||||||||||||||||||||||||||
Atomic model building | B value: 147.12 / Space: REAL / Target criteria: Correlation coefficient | ||||||||||||||||||||||||||||||||||||
Atomic model building | PDB-ID: 3UKM Accession code: 3UKM / Source name: PDB / Type: experimental model | ||||||||||||||||||||||||||||||||||||
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