Ion selectivity in a semisynthetic K⁺ channel locked in the conductive conformation

Potassium channels are K⁺-selective protein pores in cell membrane. The selectivity filter is the functional unit that allows K ⁺ channels to distinguish potassium (K⁺) and sodium (Na⁺) ions. The filter's structure depends on whether K⁺ or Na⁺ ions are bound inside it. We synthesized a K⁺ channel containing the D-enantiomer of alanine in place of a conserved glycine and found by x-ray crystallography that its filter maintains the K⁺ (conductive) structure in the presence of Na⁺ and very low concentrations of K⁺. This channel conducts Na⁺ in the absence of K⁺ but not in the presence of K⁺. These findings demonstrate that the ability of the channel to adapt its structure differently to K⁺ and Na⁺ is a fundamental aspect of ion selectivity, as is the ability of multiple K⁺ ions to compete effectively with Na⁺ for the conductive filter.