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-Structure paper
タイトル | Structural Basis for pH-gating of the K channel TWIK1 at the selectivity filter. |
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ジャーナル・号・ページ | Nat Commun, Vol. 13, Issue 1, Page 3232, Year 2022 |
掲載日 | 2022年6月9日 |
著者 | Toby S Turney / Vivian Li / Stephen G Brohawn / |
PubMed 要旨 | 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. |
リンク | Nat Commun / PubMed:35680900 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 3.33 - 3.43 Å |
構造データ | EMDB-25168, PDB-7sk0: EMDB-25169, PDB-7sk1: |
化合物 | ChemComp-OCT: ChemComp-K: ChemComp-C14: |
由来 |
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キーワード | TRANSPORT PROTEIN (運搬体タンパク質) / K+ ion Channel / pH / K+ Channel (カリウムチャネル) |