Structure of the human K_2P13.1(THIK-1) channel reveals a novel hydrophilic pore restriction and lipid cofactor site.

ABSTRACT: The halothane-inhibited K_2P leak potassium channel K_2P13.1 (THIK-1)^1-3 is found in diverse cells^1,4 including neurons^1,5 and microglia^6-8 where it affects surveillance6, synaptic pruning7, phagocytosis7, and inflammasome-mediated interleukin-1β release^6,8,9. As with many K_2Ps^1,5,10-14 and other voltage-gated ion channel (VGIC) superfamily members^3,15,16, polyunsaturated fatty acid (PUFA) lipids modulate K_2P13.1 (THIK-1)^1,5,14,17 via a poorly understood mechanism. Here, we present cryo-electronmicroscopy (cryo-EM) structures of human K_2P13.1 (THIK-1) and mutants in lipid nanodiscs and detergent. These reveal that, unlike other K_2Ps^13,

SUBMITTER: Roy-Chowdhury S 

PROVIDER: S-EPMC11230452 | biostudies-literature | 2024 Jun

REPOSITORIES: biostudies-literature