A structural link between inactivation and block of a K+ channel

Christian Ader, Robert Schneider, Sönke Hornig, Phanindra Velisetty, Erica M. Wilson, Adam Lange, Karin Giller, Iris Ohmert, Marie France Martin-Eauclaire, Dirk Trauner, Stefan Becker, Olaf Pongs, Marc Baldus

Research output: Contribution to journalArticlepeer-review

Abstract

Gating the ion-permeation pathway in K+ channels requires conformational changes in activation and inactivation gates. Here we have investigated the structural alterations associated with pH-dependent inactivation gating of the KcsA-Kv1.3 K+ channel using solid-state NMR spectroscopy in direct reference to electrophysiological and pharmacological experiments. Transition of the KcsA-Kv1.3 K+ channel from a closed state at pH 7.5 to an inactivated state at pH 4.0 revealed distinct structural changes within the pore, correlated with activation-gate opening and inactivation-gate closing. In the inactivated K+ channel, the selectivity filter adopts a nonconductive structure that was also induced by binding of a pore-blocking tetraphenylporphyrin derivative. The results establish a structural link between inactivation and block of a K+ channel in a membrane setting.

Original languageEnglish (US)
Pages (from-to)605-612
Number of pages8
JournalNature Structural and Molecular Biology
Volume15
Issue number6
DOIs
StatePublished - Jun 2008

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

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