A lipid plug affects K<sub>2P</sub>6.1(TWIK-2) function.
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ABSTRACT: Lipids are integral to ion channel function yet delineating mechanisms by which they affect function remains challenging. Within the K2P family of leak potassium channels1-3, observation of tubular densities interpreted as alkyl chains occupying lateral fenestrations linking the pore and bilayer4-8 raised the possibility that lipid access from the bilayer acts as a regulatory mechanism4-7. Here, we present cryo-electron microscopy (cryo-EM) structures of the human leak potassium channel K2P6.1 (TWIK2)9-11 and mutants in nanodisc and detergent environments that reveal an unusual conformation in the first selectivity filter (SF1) and a pair of two-chain lipids within the channel cavity (denoted the 'lipid plug'). The chains of
SUBMITTER: Mondal A
PROVIDER: S-EPMC12259115 | biostudies-literature | 2025 Jun
REPOSITORIES: biostudies-literature
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