High Resolution Structure of the Open NaK Channel

We report the crystal structure of the non-selective cation channel NaK from b. cereus at a resolution of 1.6 Å. The structure reveals the intracellular gate in an open state compared to the closed form reported previously, making NaK the only channel for which the three-dimensional structures of both conformations are known. Channel opening follows a conserved mechanism of inner helix bending utilizing a flexible glycine residue, the gating hinge, seen in MthK and most other tetrameric cation channels. Additionally, distinct inter and intra-subunit rearrangements involved in channel gating are seen and characterized for the first time along with inner helix twisting motions. Furthermore, we identify a residue deeper within the cavity of the channel pore, Phe92, which likely forms a constriction point within the open pore, restricting ion flux through the channel. Mutating this residue to Ala causes a subsequent increase in ion conduction rates as measured by (86)Rb flux assays. The structures of both the open and closed conformations of the NaK channel correlate very well with those of equivalent K(+) channel conformations, namely MthK and KcsA, respectively.