Chakrapani, Sudha; Cordero-Morales, Julio F.; Jogini, Vishwanath; Pan, Albert C.; Cortes, D. Marien; Roux, Benoit; Perozo, Eduardo
On the structural basis of modal gating behavior in K+ channels
NATURE STRUCTURAL & MOLECULAR BIOLOGY, 18:67-+, JAN 2011

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.

DOI:10.1038/nsmb.1968

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