Contributions of the central hydrophobic residue in the PXP motif of voltage-dependent K+ channels to S6 flexibility and gating properties

Abstract

Voltage-gated K+ channels are composed of four subunits each of which contains a voltage-sensing domain (S1-S4) and a pore domain (S5-P loop-S6). The exact molecular mechanisms underlying the opening and closing of the channel pore are still unclear, although evidence suggests that this process involves pivoting bending of the inner pore-lining S6 segments at the “helix-bundle crossing”. Shaker-like (Kv1.1) channels contain a highly conserved Pro-Val-Pro (PVP) motif at the base of S6 that produces a kink in the S6 helices and provides a flexible element thought to be essential for channel gating.