Atomic structure of a Na⁺- and K⁺-conducting channel

Abstract

Ion selectivity is one of the basic properties that define an ion channel. Most tetrameric cation channels, which include the K⁺, Ca²⁺, Na⁺ and cyclic nucleotide-gated channels, probably share a similar overall architecture in their ion-conduction pore, but the structural details that determine ion selection are different. Although K⁺ channel selectivity has been well studied from a structural perspective^1,2, little is known about the structure of other cation channels. Here we present crystal structures of the NaK channel from Bacillus cereus, a non-selective tetrameric cation channel, in its Na⁺- and K⁺-bound states at 2.4 Å and 2.8 Å resolution, respectively. The NaK channel shares high sequence homology and a similar overall structure with the bacterial KcsA K⁺ channel, but its selectivity filter adopts a different architecture. Unlike a K⁺ channel selectivity filter, which contains four equivalent K⁺-binding sites, the selectivity filter of the NaK channel preserves the two cation-binding sites equivalent to sites 3 and 4 of a K⁺ channel, whereas the region corresponding to sites 1 and 2 of a K⁺ channel becomes a vestibule in which ions can diffuse but not bind specifically. Functional analysis using an ⁸⁶Rb flux assay shows that the NaK channel can conduct both Na⁺ and K⁺ ions. We conclude that the sequence of the NaK selectivity filter resembles that of a cyclic nucleotide-gated channel and its structure may represent that of a cyclic nucleotide-gated channel pore.