Interior pH-sensing residue of human voltage-gated proton channel H_v1 is histidine 168.

ABSTRACT: The molecular mechanisms governing the human voltage-gated proton channel hH_v1 remain elusive. Here, we used membrane-enabled hybrid-solvent continuous constant pH molecular dynamics (CpHMD) simulations with pH replica exchange to further evaluate the structural models of hH_v1 in the closed (hyperpolarized) and open (depolarized) states recently obtained with MD simulations and explore potential pH-sensing residues. The CpHMD titration at a set of symmetric pH conditions revealed three residues that can gain or lose protons upon channel depolarization. Among them, residue H168 at the intracellular end of the S3 helix switches from the deprotonated to the protonated state and its protonation is correlated with the increased tilting of the S3 helix during the transition

SUBMITTER: Shen M 

PROVIDER: S-EPMC11700365 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature