ABSTRACT
In the beginning of the CRAC/SOC channel analysis, these channels were studied and characterized using mainly cells of the immune system, that is, T-lymphocytes and mast cells. The Orai family consists of three homologous proteins named Orai1, Orai2, and Orai3, which reside in the PM and represent Ca2+-selective ion channels allowing Ca2+ influx upon stimulation. After the initial characterization of STIM and Orai with limited structural knowledge based on bioinformatics predictions, in 2012, the crystal structures of cytosolic fragments of STIM1 and full-length Orai were reported, allowing new and more focused studies of STIM1 and Orai related to their intra- and intermolecular interactions. The small Orai-activating fragment CAD has been shown to directly bind to the Orai1 C-terminus, which seems to be the major interaction site between these two proteins. Regarding STIM1, different cytosolic C-terminal parts including a portion and the whole CAD/SOAR domain have been characterized by NMR and x-ray crystallography, revealing significant differences in their 3D atomic structures.
