Fig. 7: Activation mechanism.

a Cartoon depiction of the activation mechanism. The states are as in Fig. 1d. Inset (top) shows a schematic representation of the energy maxima in the gate region between connected states. The relative location of the transition states was obtained from phi value analysis. The two alternative pathways for activation at physiological and at high Ca²⁺ concentrations are indicated. b Schematic depiction of the relationship between residues of the gate region in different steps during activation. The view is from the extracellular side. Gate residues located on α4 (Ile 550 and Ile 551) retain their interaction with the gate residue Ile 641 on α6 in the transition between the three closed conformations although the interaction between Ile 551 and Ile 641 successively weakens until it is replaced by an interaction with Gln 649 upon transition into the open state where the gate has dissociated and the pore has dilated to permit ion conduction.