Article: K+ Conduction in the Selectivity Filter of Potassium Channels Is Monitored by the Charge Distribution along Their Sequence

ABSTRACT

Potassium channels display a high conservation of sequence of the selectivity filter (SF), yet nature has designed a variety of channels that present a wide range of absolute rates of K+ permeation. In KcsA, the structural archetype for K channels, under physiological concentrations, two K+ ions reside in the SF in configurations 1,3 (up state) and 2,4 (down state) and ion conduction is believed to follow a throughput cycle involving a transition between these states. Using free-energy calculations of KcsA, Kv1.2, and mutant channels, we show that this transition is characterized by a channel-dependent energy barrier. This barrier is strongly influenced by the charges partitioned ...

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