Structural Analysis of Ion Selectivity in the NaK Channel

Here, we present a detailed characterization of ion binding in the NaK pore using the high resolution structures of NaK in complex with various cations. These structures reveal four ion binding sites with similar chemical environments but vastly different ion preference. The most non selective of all is site 3, which is formed exclusively by backbone carbonyl oxygen atoms and resides deep within the selectivity filter. Additionally, four water molecules in combination with four backbone carbonyl oxygen atoms are seen to participate in K(+) and Rb(+) ion chelation both at the external entrance and vestibule of the NaK filter, confirming the preference for an octahedral ligand configuration for K(+) and Rb(+) binding. In contrast, Na(+) binding in the NaK filter, particularly at site 4, utilizes a pyramidal ligand configuration requiring the participation of a water molecule in the cavity. Therefore, the ability of the NaK filter to bind both Na(+) and K(+) ions seemingly arises from the ions' ability to utilize the existing environment in unique ways rather than any structural rearrangements of the filter itself.