A multipoint hydrogen-bond network underlying KcsA C-type inactivation

Julio Cordero-Morales, Vishwanath Jogini, Sudha Chakrapani, Eduardo Perozo

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

In the prokaryotic potassium channel KcsA activation gating at the inner bundle gate is followed by C-type inactivation at the selectivity filter. Entry into the C-type inactivated state has been directly linked to the strength of the H-bond interaction between residues Glu-71 and Asp-80 behind the filter, and is allosterically triggered by the rearrangement of the inner bundle gate. Here, we show that H-bond pairing between residues Trp-67 and Asp-80, conserved in most K+ channels, constitutes another critical interaction that determines the rate and extent of KcsA C-type inactivation. Disruption of the equivalent interaction in Shaker (Trp-434-Asp-447) and Kv1.2 (Trp-366-Asp-379) leads also to modulation of the inactivation process, suggesting that these residues also play an analogous role in the inactivation gating of Kv channels. The present results show that in KcsA C-type inactivation gating is governed by a multipoint hydrogen-bond network formed by the triad Trp-67-Glu71-Asp-80. This triad exerts a critical role in the dynamics and conformational stability of the selectivity filter and might serve as a general modulator of selectivity filter gating in other members of the K+ channel family.

Original languageEnglish (US)
Pages (from-to)2387-2393
Number of pages7
JournalBiophysical Journal
Volume100
Issue number10
DOIs
StatePublished - May 18 2011

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Hydrogen
prokaryotic potassium channel

All Science Journal Classification (ASJC) codes

  • Biophysics

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A multipoint hydrogen-bond network underlying KcsA C-type inactivation. / Cordero-Morales, Julio; Jogini, Vishwanath; Chakrapani, Sudha; Perozo, Eduardo.

In: Biophysical Journal, Vol. 100, No. 10, 18.05.2011, p. 2387-2393.

Research output: Contribution to journalArticle

Cordero-Morales, Julio ; Jogini, Vishwanath ; Chakrapani, Sudha ; Perozo, Eduardo. / A multipoint hydrogen-bond network underlying KcsA C-type inactivation. In: Biophysical Journal. 2011 ; Vol. 100, No. 10. pp. 2387-2393.
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