8K1V

Human TWIK-related acid-sensitive potassium channel TASK3 at pH 7.4, 5 mM KCl and 135 mM NaCl

Summary for 8K1V

• Entry DOI: 10.2210/pdb8k1v/pdb
• EMDB information: 36805
• Descriptor: Potassium channel subfamily K member 9, CHOLESTEROL HEMISUCCINATE, POTASSIUM ION, ... (4 entities in total)
• Functional Keywords: acid-sensitive, potassium ion channel, c-type, gating mechanism, membrane protein
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 65462.32

Authors

Chen, S.,Lin, H. (deposition date: 2023-07-11, release date: 2024-04-17, Last modification date: 2024-05-01)

Primary citation

Lin, H.,Li, J.,Zhang, Q.,Yang, H.,Chen, S.
C-type inactivation and proton modulation mechanisms of the TASK3 channel.
Proc.Natl.Acad.Sci.USA, 121:e2320345121-e2320345121, 2024

PubMed 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 conformational equilibrium between the conductive and C-type inactivated SF toward the latter by engaging a cation-π interaction with Trp78, consistent with molecular dynamics simulations and electrophysiological experiments. Our work illustrated how TASK3 is gated in response to extracellular pH change and implies how physiological stimuli might directly modulate the C-type gating of K2P channels.

PubMed: 38630723
DOI: 10.1073/pnas.2320345121

Experimental method

ELECTRON MICROSCOPY (3.48 Å)