An arginine residue in the outer segment of hASIC1a TM1 affects both proton affinity and channel desensitization.

ABSTRACT: Acid-sensing ion channels (ASICs) respond to changes in pH in the central and peripheral nervous systems and participate in synaptic plasticity and pain perception. Understanding the proton-mediated gating mechanism remains elusive despite the of their structures in various conformational states. We report here that R64, an arginine located in the outer segment of the first transmembrane domain of all three isoforms of mammalian ASICs, markedly impacts the apparent proton affinity of activation and the degree of desensitization from the open and preopen states. Rosetta calculations of free energy changes predict that substitutions of R64 in hASIC1a by aromatic residues destabilize the closed conformation while stabilizing the open conformation. Accordingly, F64 enhances the efficacy of pro

SUBMITTER: Chen Z 

PROVIDER: S-EPMC8050794 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature