Article abstract
Nature Structural & Molecular Biology 14, 1062 - 1069 (2007)
Published online: 7 October 2007 | doi:10.1038/nsmb1309
Molecular driving forces determining potassium channel slow inactivation
Julio F Cordero-Morales1,2,3, Vishwanath Jogini2,3, Anthony Lewis2, Valeria Vásquez1,2, D Marien Cortes2, Benoît Roux2 & Eduardo Perozo2
Abstract
K+ channels undergo a time-dependent slow inactivation process that plays a key role in modulating cellular excitability. Here we show that in the prokaryotic proton-gated K+ channel KcsA, the number and strength of hydrogen bonds between residues in the selectivity filter and its adjacent pore helix determine the rate and extent of C-type inactivation. Upon channel activation, the interaction between residues at positions Glu71 and Asp80 promotes filter constriction parallel to the permeation pathway, which affects K+-binding sites and presumably abrogates ion conduction. Coupling between these two positions results in a quantitative correlation between their interaction strength and the stability of the inactivated state. Engineering of these interactions in the eukaryotic voltage-dependent K+ channel Kv1.2 suggests that a similar mechanistic principle applies to other K+ channels. These observations provide a plausible physical framework for understanding C-type inactivation in K+ channels.
- Department of Molecular Physiology and Biological Physics, University of Virginia, 1300 JPA, Charlottesville, Virginia 22908, USA.
- Institute for Molecular Pediatric Sciences, Institute for Biophysical Dynamics and Department of Biochemistry and Molecular Biology, The University of Chicago, 929 E. 57th Street, Chicago, Illinois 60637, USA.
- These authors contributed equally to this work.
Correspondence to: Eduardo Perozo2 e-mail: eperozo@uchicago.edu
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