Molecular driving forces determining potassium channel slow inactivation

Julio Cordero-Morales, Vishwanath Jogini, Anthony Lewis, Valeria Vasquez, D. Marien Cortes, Benoît Roux, Eduardo Perozo

Research output: Contribution to journalArticle

166 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1062-1069
Number of pages8
JournalNature Structural and Molecular Biology
Volume14
Issue number11
DOIs
StatePublished - Nov 1 2007

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Kv1.2 Potassium Channel
Potassium Channels
Constriction
Protons
Hydrogen
Binding Sites
Ions

All Science Journal Classification (ASJC) codes

  • Structural Biology
  • Molecular Biology

Cite this

Molecular driving forces determining potassium channel slow inactivation. / Cordero-Morales, Julio; Jogini, Vishwanath; Lewis, Anthony; Vasquez, Valeria; Cortes, D. Marien; Roux, Benoît; Perozo, Eduardo.

In: Nature Structural and Molecular Biology, Vol. 14, No. 11, 01.11.2007, p. 1062-1069.

Research output: Contribution to journalArticle

Cordero-Morales, Julio ; Jogini, Vishwanath ; Lewis, Anthony ; Vasquez, Valeria ; Cortes, D. Marien ; Roux, Benoît ; Perozo, Eduardo. / Molecular driving forces determining potassium channel slow inactivation. In: Nature Structural and Molecular Biology. 2007 ; Vol. 14, No. 11. pp. 1062-1069.
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