On the structural basis of modal gating behavior in K(+) channels
By Sudha Chakrapani, Julio F Cordero-Morales, Vishwanath Jogini, Albert C Pan, D Marien Cortes, Benoît Roux, and Eduardo Perozo
Published in Nature Structural & Molecular Biology 18(1): 67-74 on Jan, 2011.
PMID: 21186363. PMCID: PMC3059741. Link to Pubmed page.
Project: Dynamics of Ion Permeation and Conformational Coupling in – KcsA. Core Facility: Computational Modeling.
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.