Fig. 4: Iris-like rotation of hEag2 pore domain and S5 during voltage activation.

a–d Structure comparison of S4–S5 linker (aa337–aa347) of hEag2 between the closed state (a), the pre-open state (b), and open state (c). d is an overlay view of the three states of the S4–S5 linker. e Structure comparison of pore domain, VSD and S4–S5 linker of hEag2 between the closed state and the pre-open state. f Structure comparison of pore domain, VSD and S4-S5 linker of hEag2 between the closed state and the open state. g Superposition of hEag2 pore domain, VSD and S4–S5 linker in the closed state, pre-open state, and open state. h Enlarged top view of extracellular pore domain and S5 of hEag2 in closed state and pre-open state. i Enlarged top view of the pore domain and S5 of hEag2 in the closed state and pre-open state. The rotated direction and angle of the pore domain and S5 are labeled. Closed state is colored yellow, the pre-open state is colored slate, the open state is colored green and pore dilation but the non-conducting state is colored cyan. j Representative electrophysiological recording of K337A with the voltage-pulse protocol shown underlying. Tail currents used to generate activation curves are indicated. The red trace stands for the current recorded at the holding potential of 0 mV. k Normalized tail currents I/I_max versus voltage (I–V plot) from wild type and j were plotted and fit with a Boltzmann equation.