Domain reorientation and rotation of an intracellular assembly regulate conduction in Kir potassium channels.
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.
Clarke
Oliver B
OB
The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia.
Caputo
Alessandro T
AT
Hill
Adam P
AP
Vandenberg
Jamie I
JI
Smith
Brian J
BJ
Gulbis
Jacqueline M
JM
D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry* / Q000302:isolation & purification; D001665:Binding Sites; D018360:Crystallography, X-Ray; D004926:Escherichia coli / Q000235:genetics; D042201:Magnetospirillum / Q000737:chemistry*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010743:Phospholipids / Q000737:chemistry; D011073:Polyamines / Q000737:chemistry; D011487:Protein Conformation; D054340:Receptors, KIR / Q000737:chemistry* / Q000302:isolation & purification; D011994:Recombinant Proteins / Q000737:chemistry / Q000302:isolation & purification; D016415:Sequence Alignment
D001426:Bacterial Proteins; D010743:Phospholipids; D011073:Polyamines; D054340:Receptors, KIR; D011994:Recombinant Proteins