Energetic Coupling Between Amino Acids in the pH-Sensing Region of the KcsA Channel

Abstract

The bacterial potassium channel KcsA is gated by high concentrations of intracellular protons, allowing the channel to open at pH < 5.5. Replacing key ionizable residues from the N and C termini of KcsA with residues mimicking their protonated counterparts with respect to charge renders the channel open up to pH 9.0 (Thompson et al., 2008). We proposed that these residues function as the proton-binding sites. At neutral pH they form a complex network of inter- and intrasubunit salt bridges and hydrogen bonds near the bundle crossing, stabilizing the closed state.