KCNQ1 structure and gating energy landscape. (A) Kv1.2/KCNQ1 alignment. Symbols: *, identical; :, conserved; ., semi-conserved substitutions. Red residues are charged. (B) Top-down (extracellular) view of the all-atom system. Each of the four channel subunits (consisting of S1–S6 segments) is color coded. Pore regions (S5–S6) of one subunit interact with the adjacent subunit voltage-sensing region (S1–S4). (C) S4 translation and rotation. β carbon of R4 labeled with red beads shows motion. Arrows indicate stable configurations (labeled). Yellow, S1; red, S2; white, S3; green, S4; blue, S5. (D) Implicit membrane. Isocontours at dielectric constant ε = 78 (blue) and ε = 2 (transparent) show the transition region representing the lipid esters. Water (blue) can penetrate the protein and is represented by ε = 78. (E) Energy landscape at Vm = 0 mV and associated conformations. Increasing translation corresponds to movement toward the intracellular space; increasing rotation is counterclockwise as viewed from extracellular space. Left of dotted white line is permissive (open) state. (F) Vm. Water penetration causes significant perturbation of the electric field (ripples in the potential lines; arrow). (G) Energy landscape at positive (60 mV) and negative (−80 mV) Vm. Triangles are mean S4 position (red) and standard deviation (blue). Modified from Silva et al (2009).
