The STIM1-binding site nexus remotely controls Orai1 channel gating

The ubiquitously expressed Orai Ca 2+ channels are gated through a unique process of intermembrane coupling with the Ca 2+ -sensing STIM proteins. Despite the significance of Orai1-mediated Ca 2+ signals, how gating of Orai1 is triggered by STIM1 remains unknown. A widely held gating model invokes STIM1 binding directly to Orai1 pore-forming helix. Here we report that an Orai1 C-terminal STIM1-binding site, situated far from the N-terminal pore...