Key result
E71A mutation in KcsA heterotetramers suggests channel inactivation is a cooperative process.
Why the study?
Inactivation of the KcsA potassium channel is modulated by interactions within each protomer, but the cooperative nature of this process is not fully understood.
The study provides mechanistic insights into the cooperative nature of potassium channel inactivation using KcsA heterotetramers.
Reveals pore helix network stabilizing KcsA selectivity filter; leaves open whether analogous interactions modulate human cardiac K+ channels.
The tetrameric prokaryotic potassium channel KcsA is activated by protons acting on the intracellular aspect of the protein and inactivated through conformational changes in the selectivity filter. Inactivation is modulated by a network of interactions within each protomer between the pore helix and residues at the external entrance of the channel. Inactivation is suppressed by the E71A mutation, which perturbs the stability of this network. Here, cell-free protein synthesis followed by protein purification by sodium dodecyl sulfate-polyacrylamide gel electrophoresis was used to produce heterotetramers of KcsA that contain different combinations of wild-type and E71A subunits. Single-channel recordings from these heterotetramers reveal how the network of interactions in individual protomers affects ionic conduction and channel inactivation, suggesting that the latter is a cooperative process.
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Rotem et al. (2009) studied this question. Heterotetramers of KcsA with wild-type and E71A subunits was evaluated on Ionic conduction and channel inactivation. Single-channel recordings of KcsA heterotetramers containing wild-type and E71A subunits suggest that channel inactivation is a cooperative process.
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