A key amino acid in STIM1 mediates coupling to gate the Orai1 channel

The mechanism by which STIM1 binds to gate the Orai1 channel has been intensively investigated. We recently revealed that STIM1 remotely gates the Orai1 channel through binding exclusively to the C-terminus of the Orai1 protein. This binding causes a configurational change in the C-terminal TM4-extension helix of Orai1 that is propagated through the TM4 “nexus” and the other TM helices to induce an opening of the TM1 pore-forming helix resulting in channel opening. We reveal here that the apical region of the STIM/Orai-activating region (SOAR) plays a critical role in both binding and gating of the Orai1 channel.