Molecular Basis of Tetramerization and pH-Gating in the KcsA Potassium Channel Cytoplasmic Domain

The intracellular C-terminal domain (CTD) of KcsA, a bacterial homotetrameric potassium channel, is a 40-residue long segment which natively adopts a helical bundle conformation with four-fold symmetry. A hallmark of KcsA behavior is a pH-induced conformational change which leads to opening of the channel at acidic pH. While crystal structures of full-length KcsA failed to observe a pH-effect upon the CTD, other biophysical methods have presented evidence to the contrary. We approached the question of CTD structure and its pH-dependence by studying the behavior of soluble peptides corresponding to residues 128-160 of the CTD (CTD34).