Proton-modulated interactions of ions with transport sites of prokaryotic and eukaryotic NCX prototypes.

ABSTRACT: The cytosolic pH decline from 7.2 to 6.9 results in 90% inactivation of mammalian Na⁺/Ca²⁺ exchangers (NCXs) due to protons interactions with regulatory and transport domains ("proton block"). Remarkably, the pH titration curves of mammalian and prokaryotic NCXs significantly differ, even after excluding the allosteric effects through regulatory domains. This is fascinating since "only" three (out of twelve) ion-coordinating residues (T50S, E213D, and D240N) differ between the archaeal NCX_Mj and mammalian NCXs although they contain either three or two carboxylates, respectively. To resolve the underlying mechanisms of pH-dependent regulation, the ion-coordinating residues of NCX_Mj were mutated to imitate the ion ligation arrays of mammalian NCXs; the mutational effe

SUBMITTER: Refaeli B 

PROVIDER: S-EPMC8986329 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature