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 journalArticle

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

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Magnetic Resonance Spectroscopy
Pharmacology
Ions
Membranes
tetraphenylporphyrin

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

Cite this

Ader, C., Schneider, R., Hornig, S., Velisetty, P., Wilson, E. M., Lange, A., ... Baldus, M. (2008). A structural link between inactivation and block of a K+ channel. Nature Structural and Molecular Biology, 15(6), 605-612. https://doi.org/10.1038/nsmb.1430

A structural link between inactivation and block of a K+ channel. / Ader, Christian; Schneider, Robert; Hornig, Sönke; Velisetty, Phanindra; Wilson, Erica M.; Lange, Adam; Giller, Karin; Ohmert, Iris; Martin-Eauclaire, Marie France; Trauner, Dirk; Becker, Stefan; Pongs, Olaf; Baldus, Marc.

In: Nature Structural and Molecular Biology, Vol. 15, No. 6, 06.2008, p. 605-612.

Research output: Contribution to journalArticle

Ader, C, Schneider, R, Hornig, S, Velisetty, P, Wilson, EM, Lange, A, Giller, K, Ohmert, I, Martin-Eauclaire, MF, Trauner, D, Becker, S, Pongs, O & Baldus, M 2008, 'A structural link between inactivation and block of a K+ channel', Nature Structural and Molecular Biology, vol. 15, no. 6, pp. 605-612. https://doi.org/10.1038/nsmb.1430
Ader C, Schneider R, Hornig S, Velisetty P, Wilson EM, Lange A et al. A structural link between inactivation and block of a K+ channel. Nature Structural and Molecular Biology. 2008 Jun;15(6):605-612. https://doi.org/10.1038/nsmb.1430
Ader, Christian ; Schneider, Robert ; Hornig, Sönke ; Velisetty, Phanindra ; Wilson, Erica M. ; Lange, Adam ; Giller, Karin ; Ohmert, Iris ; Martin-Eauclaire, Marie France ; Trauner, Dirk ; Becker, Stefan ; Pongs, Olaf ; Baldus, Marc. / A structural link between inactivation and block of a K+ channel. In: Nature Structural and Molecular Biology. 2008 ; Vol. 15, No. 6. pp. 605-612.
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