Figure 6. The CTD-mediated ‘switch’ gating mechanism.

In the naive closed state (C₀), the distal CTD is stretched around the β_CD via a salt bridge ‘hook’ interaction with the ARD and the switch is ‘off’. When the CTD is ‘unhooked’ from the ARD, it undergoes a coil-to-helix transition (the switch turns ‘on’) which leads to a conformational change in the loop of AR5 and consequently to increased coupling between the cytoplasmic and transmembrane domains, which is prerequisite for channel opening (C₁).