A Highly Charged Voltage-Sensor Helix Spontaneously Translocates across Membranes

摘要

The molecular mechanism of gating in voltage-gated potassium channels lies at the intersection of biochemistry, structural biology, and neurobiology, and for that reason it has been studied intensively. The first complete structure of a voltage-gated potassium channel, the K_VAP protein from the archeon Aeropyrum pernix, was solved in 2003. Based on that structure and on biochemical data a controversial model was proposed for voltage gating that, surprisingly, placed the four arginine residues of the voltage-sensing "S4 helix" in direct contact with the lipid environment. Furthermore, it was hypothesized that the S4 segment moved a distance of 20 A across the membrane during channel gating; this hypothesis is in direct disagreement with the idea that the hydrocarbon core of the bilayer will impart a strict barrier to charged moieties in general, and to the guanidinyl moiety of arginine in particular. Herein, we use synthetic peptides to test the critical idea that the physical properties of the S4 sequence alone are sufficient to allow it to move easily across lipid bilayer membranes.