Cooperative Binding of Stromal Interaction Molecule 1 (STIM1) to the N and C Termini of Calcium Release-Activated Calcium Modulator 1 (Orai1) [Membrane Biology]
November 6th, 2015 by Palty, R., Isacoff, E. Y.
Calcium flux through store operated calcium entry (SOCE) is a central regulator of intracellular calcium signaling. The two key components of the store operated calcium release activated calcium (CRAC) channel are the Ca2+ sensing protein stromal interaction molecule 1 (STIM1) and the channel pore forming protein Orai1. During SOCE activation calcium depletion from the endoplasmic reticulum triggers a series of conformational changes in STIM1 that unmask a minimal Orai1 activating domain (CAD). In order to gate Orai1 channels the exposed STIM1 activating domain binds to two sites in Orai1, one in the N terminus and one in the C terminus. Whether the two sites operate as distinct binding domains or cooperate in CAD binding is unknown. In this study we show that the N and C terminal domains of Orai1 synergistically contribute to interaction with STIM1 and couple STIM1 binding with channel gating and modulation of ion selectivity.