Physiological CRAC channel activation and pore properties require STIM1 binding to all six Orai1 subunits.

ABSTRACT: The binding of STIM1 to Orai1 controls the opening of store-operated CRAC channels as well as their extremely high Ca²⁺ selectivity. Although STIM1 dimers are known to bind directly to the cytosolic C termini of the six Orai1 subunits (SUs) that form the channel hexamer, the dependence of channel activation and selectivity on the number of occupied binding sites is not well understood. Here we address these questions using dimeric and hexameric Orai1 concatemers in which L273D mutations were introduced to inhibit STIM1 binding to specific Orai1 SUs. By measuring FRET between fluorescently labeled STIM1 and Orai1, we find that homomeric L273D mutant channels fail to bind STIM1 appreciably; however, the L273D SU does bind STIM1 and contribute to channel activation when located adj

SUBMITTER: Yen M 

PROVIDER: S-EPMC6168240 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature