Absence of Ion-Binding Affinity in the Putatively Inactivated Low-[K+] Structure of the KcsA Potassium Channel

Potassium channels are membrane proteins that selectively conduct K+ across cellular membranes. The narrowest part of their pore, the selectivity filter, is responsible for distinguishing K+ from Na+, and can also act as a gate through a mechanism known as C-type inactivation. It has been proposed that a conformation of the KcsA channel obtained by crystallization in presence of low concentration of K+ (PDB 1K4D) could correspond to the C-type inactivated state. Here, we show using molecular mechanics simulations that such conformation has little ion-binding affinity and that ions do not contribute to its stability. The simulations suggest that, in this conformation, the selectivity filter is mostly occupied by water molecules. Whether such ion-free state of the KcsA channel is physiologically accessible and representative of the inactivated state of eukaryotic channels remains unclear.