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Nat Struct Mol Biol. 2011 Jan;18(1):67-74. doi: 10.1038/nsmb.1968. Epub 2010 Dec 26.

On the structural basis of modal gating behavior in K(+) channels.

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Department of Biochemistry and Molecular Biology, University of Chicago, Center for Integrative Science, Chicago, Illinois, USA.


Modal-gating shifts represent an effective regulatory mechanism by which ion channels control the extent and time course of ionic fluxes. Under steady-state conditions, the K(+) channel KcsA shows three distinct gating modes, high-P(o), low-P(o) and a high-frequency flicker mode, each with about an order of magnitude difference in their mean open times. Here we show that in the absence of C-type inactivation, mutations at the pore-helix position Glu71 unmask a series of kinetically distinct modes of gating in a side chain-specific way. These gating modes mirror those seen in wild-type channels and suggest that specific interactions in the side chain network surrounding the selectivity filter, in concert with ion occupancy, alter the relative stability of pre-existing conformational states of the pore. The present results highlight the key role of the selectivity filter in regulating modal gating behavior in K(+) channels.

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