Orai channel C-terminal peptides are key modulators of STIM-Orai coupling and calcium signal generation.

ABSTRACT: Junctional coupling between endoplasmic reticulum (ER) Ca²⁺-sensor STIM proteins and plasma membrane (PM) Orai channels mediates Ca²⁺ signals in most cells. We reveal that PM-tethered, fluorescently tagged C-terminal M4x (fourth transmembrane helix contains a cytoplasmic C-terminal extension) peptides from Orai channels undergo a Leu-specific signature of direct interaction with the STIM1 Orai-activating region (SOAR), exactly mimicking STIM1 binding to gate Orai channels. The 20-amino-acid Orai3-M4x peptide associates avidly with STIM1 within ER-PM junctions, functions to competitively block native Ca²⁺ signals, and mediates a key modification of STIM-Orai coupling induced by 2-aminoethoxydiphenyl borate. By blocking STIM-Orai coupling, the Orai3-M4x pepti

SUBMITTER: Baraniak JH 

PROVIDER: S-EPMC8462482 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature