Diverse gating in K+ channels: differential role of the pore-helix glutamate in stabilizing the channel pore.

The selectivity filter and adjacent regions in the bacterial KcsA and inwardly rectifying K(+) (Kir) channels reveal significant conformational changes that cause the channel pore to transition from an activated to inactive state (C-type inactivation) once the channel is open. The meshwork of residues stabilizing the pore of KcsA involves Glu71-Asp80 carboxyl-carboxylate interaction 'behind' the selectivity filter. Interestingly, the Kir channels do not have this exact interaction, but instead have a Glu-Arg salt bridge where the Glu is in the same position but the Arg is one position N-terminal compared to the Asp in KcsA. Also, the Kir channels lack the Trp that hydrogen bonds to Asp80 in KcsA. Here, the sequence and structural information are combined to understand the dissimilarity in the role of the pore-helix Glu in stabilizing the pore structure in KcsA and Kir channels. This review illustrates that although Glu is quite conserved among both types of channels, the network of interactions is not translatable from one channel to the other; thereby suggesting a unique phenomenon of diverse gating patterns in K(+) channels.