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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-25168 | |||||||||
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Title | TWIK1 in MSP1D1 lipid nanodisc at pH 7.4 | |||||||||
![]() | TWIK1 in MSP1D1 lipid nanodisc at pH 7.4 | |||||||||
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Function / homology | ![]() Tandem of pore domain in a weak inwardly rectifying K+ channels (TWIK) / Phase 4 - resting membrane potential / ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() Similarity search - Function | |||||||||
Biological species | ![]() ![]() ![]() | |||||||||
Method | ![]() ![]() | |||||||||
![]() | Turney TS / Brohawn SG | |||||||||
Funding support | ![]()
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![]() | ![]() 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: ![]() Title: Structural Basis for pH-Gating of the K + Channel TWIK1 at the Selectivity Filter Authors: Turney TS / Li V / Brohawn SG | |||||||||
History |
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Structure visualization
Movie |
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Structure viewer | EM map: ![]() ![]() ![]() |
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 2.1 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 18.3 KB 18.3 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 7.2 KB | Display | ![]() |
Images | ![]() | 40.7 KB | ||
Masks | ![]() | 30.5 MB | ![]() | |
Others | ![]() ![]() | 2.1 MB 2.1 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7sk0MC ![]() 7sk1C M: atomic model generated by this map C: citing same article ( |
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Similar structure data |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Annotation | TWIK1 in MSP1D1 lipid nanodisc at pH 7.4 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.137 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Mask #1
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Density Histograms |
-Half map: Half Map 1
File | emd_25168_half_map_1.map | ||||||||||||
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Annotation | Half Map 1 | ||||||||||||
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Density Histograms |
-Half map: Half Map 2
File | emd_25168_half_map_2.map | ||||||||||||
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Annotation | Half Map 2 | ||||||||||||
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Density Histograms |
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Sample components
-Entire : TWIK1 in MSP1D1 Lipid Nanodisc at pH 7.4
Entire | Name: TWIK1 in MSP1D1 Lipid Nanodisc at pH 7.4 |
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Components |
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-Supramolecule #1: TWIK1 in MSP1D1 Lipid Nanodisc at pH 7.4
Supramolecule | Name: TWIK1 in MSP1D1 Lipid Nanodisc at pH 7.4 / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1 |
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Source (natural) | Organism: ![]() ![]() ![]() |
Recombinant expression | Organism: ![]() ![]() |
-Macromolecule #1: Potassium channel subfamily K member 1
Macromolecule | Name: Potassium channel subfamily K member 1 / type: protein_or_peptide / ID: 1 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() ![]() |
Molecular weight | Theoretical: 38.265984 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: MLQSLAGSSC VRLVERHRSA WCFGFLVLGY LLYLVFGAVV FSSVELPYED LLRQELRKLK RRFLEEHECL SEPQLEQFLG RVLEASNYG VSVLSNASGN WNWDFTSALF FASTVLSTTG YGHTVPLSDG GKAFCIIYSV IGIPFTLLFL TAVVQRVTVH V TRRPVLYF ...String: MLQSLAGSSC VRLVERHRSA WCFGFLVLGY LLYLVFGAVV FSSVELPYED LLRQELRKLK RRFLEEHECL SEPQLEQFLG RVLEASNYG VSVLSNASGN WNWDFTSALF FASTVLSTTG YGHTVPLSDG GKAFCIIYSV IGIPFTLLFL TAVVQRVTVH V TRRPVLYF HIRWGFSKQV VAIVHAVLLG FVTVSCFFFI PAAVFSVLED DWNFLESFYF CFISLSTIGL GDYVPGEGYN QK FRELYKI GITCYLLLGL IAMLVVLETF CELHELKKFR KMFYVKKDKD EDQVHIMEHD QLSFSSITEQ AAGLKEEQKQ NEP FVASQS PPYEDGSANH |
-Macromolecule #2: N-OCTANE
Macromolecule | Name: N-OCTANE / type: ligand / ID: 2 / Number of copies: 2 / Formula: OCT |
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Molecular weight | Theoretical: 114.229 Da |
Chemical component information | ![]() ChemComp-OCT: |
-Macromolecule #3: POTASSIUM ION
Macromolecule | Name: POTASSIUM ION / type: ligand / ID: 3 / Number of copies: 5 / Formula: K |
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Molecular weight | Theoretical: 39.098 Da |
-Experimental details
-Structure determination
Method | ![]() |
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Aggregation state | particle |
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Sample preparation
Buffer | pH: 7.4 Component:
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Grid | Model: Quantifoil R1.2/1.3 / Pretreatment - Type: GLOW DISCHARGE | ||||||||||||
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277 K / Instrument: FEI VITROBOT MARK III |
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Electron microscopy
Microscope | FEI TALOS ARCTICA |
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Electron beam | Acceleration voltage: 200 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD![]() |
Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 49.715 e/Å2 |
Experimental equipment | ![]() Model: Talos Arctica / Image courtesy: FEI Company |