C-type inactivation and proton modulation mechanisms of the TASK3 channel.

ABSTRACT: The TWIK-related acid-sensitive K⁺ channel 3 (TASK3) belongs to the two-pore domain (K2P) potassium channel family, which regulates cell excitability by mediating a constitutive "leak" potassium efflux in the nervous system. Extracellular acidification inhibits TASK3 channel, but the molecular mechanism by which channel inactivation is coupled to pH decrease remains unclear. Here, we report the cryo-electron microscopy structures of human TASK3 at neutral and acidic pH. Structural comparison revealed selectivity filter (SF) rearrangements upon acidification, characteristic of C-type inactivation, but with a unique structural basis. The extracellular mouth of the SF was prominently dilated and simultaneously blocked by a hydrophobic gate. His98 protonation shifted the conformatio

SUBMITTER: Lin H 

PROVIDER: S-EPMC11046659 | biostudies-literature | 2024 Apr

REPOSITORIES: biostudies-literature