Gating and regulation of the calcium release‐activated calcium channel: Recent progress from experiments and molecular modeling

Abstract

Calcium release-activated calcium (CRAC) channels are highly calcium ion (Ca 2+)-selective channels in the plasma membrane. The transient drop of endoplasmic reticulum Ca 2+ level activates its calcium sensor stromal interaction molecule (STIM) and then triggers the gating of the CRAC channel pore unit Orai. This process involves a variety of activities of the immune system. Therefore, understanding how the activation and regulation of the CRAC channel can be accomplished is essential. Here we briefly summarize the recent progress on Orai gating and its regulation by 2-aminoethoxydiphenylborate (2-APB) obtained from structural biology studies, biochemical and electrophysiological measurements, as well as molecular modeling. Indeed, integration between experiments and computations has further deepened our understanding of the channel gating and regulation.