Fine-tuning pH sensor H98 by remote essential residues in the hydrogen-bond network of mTASK-3.

ABSTRACT: TASK-3 generates a background K⁺ conductance which when inhibited by acidification depolarizes membrane potential and increases cell excitability. These channels sense pH by protonation of histidine residue H98, but recent evidence revealed that several other amino acid residues also contribute to TASK-3 pH sensitivity, suggesting that the pH sensitivity is determined by an intermolecular network. Here we use electrophysiology and molecular modeling to characterize the nature and requisite role(s) of multiple amino acids in pH sensing by TASK-3. Our results suggest that the pH sensor H98 and consequently pH sensitivity is influenced by remote amino acids that function as a hydrogen-bonding network to modulate ionic conductivity. Among the residues in the network, E30 and K79 are

SUBMITTER: Fan X 

PROVIDER: S-EPMC11583903 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature