An aromatic amino acid in the CC1 domain plays a crucial role in the auto-inhibitory mechanism of STIM1

In this study, we first predicted a short inhibitory domain (310-317) in human STIM1 that might determine the different localizations of human and C. elegans STIM1 in resting cells. Next, we confirmed the prediction and further identified an aromatic amino acid residue Y316 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. And the introduction of Y316A mutation caused the higher-order oligolization of in vitro purified STIM1 fragment containing both auto-inhibitory domain and CAD domain. We proposed that the Y316 residue may be involved in the auto-inhibitory mechanism of STIM1-CT in the quiescent state. This inhibition could be achieved either by interacting with the CAD domain using hydrogen and/or hydrophobic bonds or by intermolecular interaction using repulsive forces, which maintained a dimeric STIM1.

Source: BJ Cell - June 25, 2013 Category: Biochemistry Authors: J Yu, H Zhang, M ZHANG, Y Deng, H Wang, J Lu, T Xu, P Xu Tags: BJ Signal Source Type: research