Key result
Unlike the KcsA channel, the MthK potassium channel selectivity filter maintains a conductive conformation at low potassium concentrations because only the central S2 site loses its ion.
Why the study?
The role of the selectivity filter in controlling potassium channel activity differs across channels, and the mechanism by which the MthK channel regulates gating at the filter was unclear.
The selectivity filters of MthK and KcsA differ in their ion affinities due to interactions behind the filter, determining their distinct inactivation phenotypes.
MthK filter gating differs from KcsA; leaves open relevance to cardiac K+ channel regulation in arrhythmias.
Significance The role of the selectivity filter in controlling potassium channel activity is different for different channels, despite identical sequences and structures. While KcsA and voltage-gated channels experience C-type inactivation by collapsing their selectivity filters under reduced potassium concentration, the mechanism by which the MthK channel regulates gating at the filter is unclear. Unlike the KcsA selectivity filter that experiences a uniform titration of its ion binding sites, leading to collapse, high-resolution X-ray structures of the pore-only MthK channel reveal that only the central S2 site loses its ion at low concentrations, insufficient for a conformational change. The selectivity filters of MthK and KcsA differ in their ion affinities due to interactions behind the filter, determining their inactivation phenotypes.
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Boiteux et al. (2020) studied this question. Potassium concentration was evaluated. Unlike the KcsA channel, the MthK potassium channel selectivity filter maintains a conductive conformation at low potassium concentrations because only the central S2 site loses its ion.
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