7SK0
TWIK1 in MSP1D1 lipid nanodisc at pH 7.4
Summary for 7SK0
| Entry DOI | 10.2210/pdb7sk0/pdb |
| EMDB information | 25168 |
| Descriptor | Potassium channel subfamily K member 1, N-OCTANE, POTASSIUM ION (3 entities in total) |
| Functional Keywords | k+ ion channel, ph, transport protein |
| Biological source | Rattus norvegicus (Rat) |
| Total number of polymer chains | 2 |
| Total formula weight | 76955.92 |
| Authors | Turney, T.S.,Brohawn, S.G. (deposition date: 2021-10-19, release date: 2021-11-24, Last modification date: 2024-10-30) |
| Primary citation | Turney, T.S.,Li, V.,Brohawn, S.G. Structural Basis for pH-gating of the K + channel TWIK1 at the selectivity filter. Nat Commun, 13:3232-3232, 2022 Cited by PubMed 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 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. PubMed: 35680900DOI: 10.1038/s41467-022-30853-z PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.33 Å) |
Structure validation
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