Potassium channel selectivity is determined by square antiprismatic ion chelation

It is established that potassium channel selectivity is provided by the selectivity filter (SF) replicating the geometry of the hydrated K⁺ ion surrounded by eight water molecules forming a square antiprism. The SF forms four K⁺-binding sites (S1-S4), each built up of eight oxygen atoms perfectly arranged in a square antiprism. This allows desolvation with no energy penalty for K⁺, but not other cations. Here, a nearly protein universe-wide geometric scanning is reported for square antiprismatic sites with an algorithm using K⁺-ion as a template. We find that the SF is a unique structure persisting in K⁺-channels and some related proteins, but it is absent from other proteins. Conductive and non-conductive SFs may be clearly delineated by a 1.25 Å RMSD threshold at sites S1-S3, providing a precise and simple criterion for the geometric assessment of the functional state of SFs involved in the processes of C-type gating or C-type inactivation. Antiprismatic sites were also predicted in different channel domains and other membrane as well as non-membrane proteins, where they may be of functional significance. It can be concluded that our geometric scanning approach is a facile tool for the assessment of ion chelation by proteins.