STIM1 triggers a gating rearrangement at the extracellular mouth of the ORAI1 channel

The plasma membrane Ca2+ channel ORAI1 is gated directly by the ER-resident protein STIM1. Here Gudlur et al. show that STIM1 elicits conformational changes near the extracellular opening of the channel, involving the Ca2+-binding residue E106 and the pore-lining residue V102, which forms a barrier to ion conduction in the closed state.