The inactivation domain of STIM1 is functionally coupled with the Orai1 pore to enable Ca2+-dependent inactivation.

ABSTRACT: The inactivation domain of STIM1 (ID(STIM): amino acids 470-491) has been described as necessary for Ca(2+)-dependent inactivation (CDI) of Ca(2+) release-activated Ca(2+) (CRAC) channels, but its mechanism of action is unknown. Here we identify acidic residues within IDSTIM that control the extent of CDI and examine functional interactions of ID(STIM) with Orai1 pore residues W76 and Y80. Alanine scanning revealed three IDSTIM residues (D476/D478/D479) that are critical for generating full CDI. Disabling ID(STIM) by a triple alanine substitution for these three residues ("STIM1 3A") or by truncation of the entire domain (STIM1(1-469)) reduced CDI to the same residual level observed for the Orai1 pore mutant W76A (approximately one third of the extent seen with full-length STIM1). Results

SUBMITTER: Mullins FM 

PROVIDER: S-EPMC4727943 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature