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Significance Crystal structures of K+ channels display 4 K+ ions bound to the selectivity filter. Two mechanistic models have been proposed to explain this experimental observation. The “canonical model” proposes 2 alternating ion-bound configurations (1,3 and 2,4) coexisting within a channel’s filter. Alternatively, in the “direct knock-on model” all binding sites are occupied at any given time, and ions establish direct contact. Here, it is shown the structure of a K+ -channel selectivity filter stabilized in the 2,4-ion configuration, which provides a definitive experimental demonstration for the canonical model of ion permeation in K+ channels. In these structures, ions are separated by water molecules that seem to be cotransported during each ion transport cycle, which is in agreement with streaming potential measurements.

Structure, function, and ion-binding properties of a K + channel stabilized in the 2,4-ion–bound configuration

Structure, function, and ion-binding properties of a K ⁺ channel stabilized in the 2,4-ion–bound configuration