Article abstract
Nature Structural & Molecular Biology 15, 605 - 612 (2008)
Published online: 18 May 2008 | doi:10.1038/nsmb.1430
A structural link between inactivation and block of a K+ channel
Christian Ader1,5, Robert Schneider1,5, Sönke Hornig2, Phanindra Velisetty2, Erica M Wilson3, Adam Lange1, Karin Giller1, Iris Ohmert2, Marie-France Martin-Eauclaire4, Dirk Trauner3, Stefan Becker1, Olaf Pongs2 & Marc Baldus1
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.
- Max-Planck Institute for Biophysical Chemistry, Department of NMR-Based Structural Biology, Am Fassberg 11, 37077 Göttingen, Germany.
- University Hospital Hamburg-Eppendorf, Center for Molecular Neurobiology, Institute for Neural Signaltransduction, Falkenried 94, 20251 Hamburg, Germany.
- Department of Chemistry, University of California, Berkeley, California 94720-1460, USA.
- Centre National de la Recherche Scientifique (CNRS) Institut Jean Roche, Université de la Méditerranée, Boulevard Pierre Dramard, 13916 Marseille Cedex 20, France.
- These authors contributed equally to this work.
Correspondence to: Dirk Trauner3 e-mail: trauner@berkeley.edu
Correspondence to: Olaf Pongs2 e-mail: morin@zmnh.uni-hamburg.de
Correspondence to: Marc Baldus1 e-mail: maba@mpibpc.mpg.de
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