@article{2501cc931e4a4b13aef1549c0afd4145,
title = "A structural link between inactivation and block of a K+ channel",
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.",
author = "Christian Ader and Robert Schneider and S{\"o}nke Hornig and Phanindra Velisetty and Wilson, {Erica M.} and Adam Lange and Karin Giller and Iris Ohmert and Martin-Eauclaire, {Marie France} and Dirk Trauner and Stefan Becker and Olaf Pongs and Marc Baldus",
note = "Funding Information: Technical assistance by B. Angerstein is gratefully acknowledged. This work was funded in part by the Deutsche Forschungsgemeinschaft (DFG; Ba 1700/9-1, Be 2345/5-1, Po 137/38-1), by a PhD fellowship to C.A. from the Stiftung Stipendien-Fonds of the Verband der Chemischen Industrie, and by a PhD fellowship to R.S. from the DFG graduate school 782 {\textquoteleft}Spectroscopy and Dynamics of Molecular Coils and Aggregates{\textquoteright}. We are indebted to R. Wagner (University of Osnabr{\"u}ck, Germany) for invaluable support in context of the lipid-bilayer reconstitution experiments. We are grateful to R. Riek for providing solution-state NMR resonance assignments of KcsA constructs in micelles.",
year = "2008",
month = jun,
doi = "10.1038/nsmb.1430",
language = "English (US)",
volume = "15",
pages = "605--612",
journal = "Nature Structural and Molecular Biology",
issn = "1545-9993",
publisher = "Nature Research",
number = "6",
}