Abstract：
:Potassium channels embedded in cell membranes employ gates to regulate K+ current. While a specific constriction in the permeation pathway has historically been implicated in gating, recent reports suggest that the signature ion selectivity filter located in the outer membrane leaflet may be equally important. Inwardly rectifying K+ channels also control the directionality of flow, using intracellular polyamines to stem ion efflux by a valve-like action. This study presents crystallographic evidence of interdependent gates in the conduction pathway and reveals the mechanism of polyamine block. Reorientation of the intracellular domains, concomitant with activation, instigates polyamine release from intracellular binding sites to block the permeation pathway. Conformational adjustments of the slide helices, achieved by rotation of the cytoplasmic assembly relative to the pore, are directly correlated to the ion configuration in the selectivity filter. Ion redistribution occurs irrespective of the constriction, suggesting a more expansive role of the selectivity filter in gating than previously appreciated.
journal_name
Celljournal_title
Cellauthors
Clarke OB,Caputo AT,Hill AP,Vandenberg JI,Smith BJ,Gulbis JMdoi
10.1016/j.cell.2010.05.003subject
Has Abstractpub_date
2010-06-11 00:00:00pages
1018-29issue
6eissn
0092-8674issn
1097-4172pii
S0092-8674(10)00501-5journal_volume
141pub_type
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