Novel insights into K⁺ selectivity from high-resolution structures of an open K⁺ channel pore.

A high-resolution structural analysis of MthK, a Ca²⁺-gated K⁺+ channel from Methanobacterium thermoautotrophicum, a methane producing bacterium. K⁺ channels are tetrameric channels that display very high selectivity for K⁺ over Na⁺, even though Na+ is a smaller ion.

This selectivity is due to the highly conserved sequence TVGYG, shown below. The molecule is a tetramer, but only one sequence is shown for clarity.


From bottom to top (N-C), Threonine, Valine, Glycine, Tyrosine, Glycine. The purple spheres represent K⁺ ions.

As can be seen in the image, there are 4 possible occupation sites for K⁺ ions, and, due to steric restrictions, it has been proposed that there are two possible configurations, 1 + 3 and 2 + 4.

This sequence forms a pore that is 11Å wide, so it can accommodate both K⁺ and Na⁺ ions into its pore. The selectivity arises from the carbonyl groups that are able to stabilise the cation as it moves through the pore. The carbonyl groups are only able to stabilise K⁺, as Na⁺ is too small to interact with all of the carbonyl groups.

This is the case for KcsA, a prototypic K⁺ channel, where conductivity is maintained by K⁺ binding. Without K⁺, or in a low K⁺/high Na⁺ environment, the pore collapses to a non-conductive state.

However, the MthK selectivity filter maintains a conductive conformation even in the absence of K⁺, and thus allows the channel to conduct Na⁺. The high-resolution structures featured in this paper show how K⁺ competes with Na⁺.