Sodium Ions Do Not Stabilize the Selectivity Filter of a Potassium Channel

Abstract

Ion conduction is an essential function for electrical activity in all organisms. The non-selective ion channel NaK was previously shown to adopt two stable conformations of the selectivity filter. Here, we present solid-state NMR measurements of NaK demonstrating a population shift between these conformations induced by changing the ions in the sample while the overall structure of NaK is not affected. We show that two K+-selective mutants (NaK2K and NaK2K-Y66F) suffer a complete loss of selectivity filter stability under Na+ conditions, but do not collapse into a defined structure. Widespread chemical shift perturbations are seen between the Na+ and K+ states of the K+-selective mutants in the region of the pore helix indicating structural changes. We conclude that the stronger link between the selectivity filter and the pore helix in the K+-selective mutants, compared to the non-selective wild-type NaK channel, reduces the ion-dependent conformational flexibility of the selectivity filter.