7SK0

TWIK1 in MSP1D1 lipid nanodisc at pH 7.4

7SK0 の概要

• エントリーDOI: 10.2210/pdb7sk0/pdb
• EMDBエントリー: 25168
• 分子名称: Potassium channel subfamily K member 1, N-OCTANE, POTASSIUM ION (3 entities in total)
• 機能のキーワード: k+ ion channel, ph, transport protein
• 由来する生物種: Rattus norvegicus (Rat)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 76955.92

構造登録者

Turney, T.S.,Brohawn, S.G. (登録日: 2021-10-19, 公開日: 2021-11-24, 最終更新日: 2024-10-30)

主引用文献

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

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: 35680900
DOI: 10.1038/s41467-022-30853-z

実験手法

ELECTRON MICROSCOPY (3.33 Å)