Structural basis for pH gating of the two-pore domain K⁺ channel TASK2.

ABSTRACT: TASK2 (also known as KCNK5) channels generate pH-gated leak-type K⁺ currents to control cellular electrical excitability^1-3. TASK2 is involved in the regulation of breathing by chemosensory neurons of the retrotrapezoid nucleus in the brainstem^4-6 and pH homeostasis by kidney proximal tubule cells^7,8. These roles depend on channel activation by intracellular and extracellular alkalization^3,8,9, but the mechanistic basis for TASK2 gating by pH is unknown. Here we present cryo-electron microscopy structures of Mus musculus TASK2 in lipid nanodiscs in open and closed conformations. We identify two gates, distinct from previously observed K⁺ channel gates, controlled by stimuli on either side of the membrane. Intracellular gatin

SUBMITTER: Li B 

PROVIDER: S-EPMC8628578 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature