Abstract
TWIK1 is a widely expressed pH-gated two-pore domain K+ channel (K2P) that contributes to cardiac rhythm generation, as well as insulin release from pancreatic beta cells. TWIK1 displays unique channel properties; including low basal activity in cells, 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 type of K+ channel gate at the selectivity filter.
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