On the stoichiometry of resting and activated CRAC channels.

STIM1 and Orai1 are two essential components of the calcium release-activated calcium (CRAC) channel. Recently, distinct stoichiometries of STIM1 to Orai1 in assembling CRAC channels are proposed based on different techniques, such as single-molecule bleaching, biochemistry, crystallography, and concatenated constructs for electrophysiological experiments. Here, we review in detail these experiments as well as the strength and weakness of methods used. We propose that the tetrameric Orai1 is the pore for the resting and activated CRAC channel, where from two to eight STIM1 proteins open the channel in a graded manner.