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- Title
An aromatic amino acid in the coiled-coil 1 domain plays a crucial role in the auto-inhibitory mechanism of STIM1.
- Authors
Junwei YU; Haining ZHANG; Mingshu ZHANG; Yongqiang DENG; Huiyu WANG; Jingze LU; Tao XU; Pingyong XU
- Abstract
STIM1 (stromal interactionmolecule 1) is one of the key elements that mediate store-operated Ca2+ entry via CRAC (Ca2+ - releaseactivated Ca2+) channels in immune and non-excitable cells. Under physiological conditions, the intramolecular auto-inhibitions in STIM1 C- and STIM1 N-termini play essential roles in keeping STIM1 in an inactive state. However, the auto-inhibitory mechanism of the STIM1 C-terminus is still unclear. In the present study, we first predicted a short inhibitory domain (residues 310-317) in human STIM1 that might determine the different localizations of human STIM1 from Caenorhabditis elegans STIM1 in resting cells. Next, we confirmed the prediction and further identified an aromatic amino acid residue, Tyr316, that played a crucial role in maintaining STIM1 in a closed conformation in quiescent cells. Full-length STIM1-Y316A formed constitutive clusters near the plasma membrane and activated the CRAC channel in the resting state when co-expressed with Orai1. The introduction of a Y316A mutation caused the higher-order oligomerization of the in vitro purified STIM1 fragment containing both the auto-inhibitory domain andCAD(CRAC-activating domain).We propose that the Tyr316 residue may be involved in the auto-inhibitory mechanism of the STIM1 C-terminus in the quiescent state. This inhibition could be achieved either by interactingwith the CADusing hydrogen and/or hydrophobic bonds, or by an intermolecular interaction using repulsive forces, which maintained a dimeric STIM1.
- Subjects
IMMUNE system; CAENORHABDITIS elegans; MEMBRANE potential; AMINO acid residues; QUIESCENT plasmas; HYDROPHOBIC interactions
- Publication
Biochemical Journal, 2013, Vol 454, Issue 3, p401
- ISSN
0264-6021
- Publication type
Article
- DOI
10.1042/BJ20130292