Transmembrane Domain 3 (TM3) Governs Orai1 and Orai3 Pore Opening in an Isoform-Specific Manner.

ABSTRACT: STIM1-mediated activation of calcium selective Orai channels is fundamental for life. The three Orai channel isoforms, Orai1-3, together with their multiple ways of interplay, ensure their highly versatile role in a variety of cellular functions and tissues in both, health and disease. While all three isoforms are activated in a store-operated manner by STIM1, they differ in diverse biophysical and structural properties. In the present study, we provide profound evidence that non-conserved residues in TM3 control together with the cytosolic loop2 region the maintenance of the closed state and the configuration of an opening-permissive channel conformation of Orai1 and Orai3 in an isoform-specific manner. Indeed, analogous amino acid substitutions of these non-conserved residues led to dist

SUBMITTER: Tiffner A 

PROVIDER: S-EPMC7905104 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature