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.
authors.affiliation: Max-Planck Institute for Biophysical Chemistry, Department of NMR-Based Structural Biology, Am Fassberg 11, 37077 Göttingen, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Ader
authors.forename: Robert
authors.initials: R
authors.lastname: Schneider
authors.forename: Sönke
authors.initials: S
authors.lastname: Hornig
authors.forename: Phanindra
authors.initials: P
authors.lastname: Velisetty
authors.forename: Erica M
authors.initials: EM
authors.lastname: Wilson
authors.forename: Adam
authors.initials: A
authors.lastname: Lange
authors.forename: Karin
authors.initials: K
authors.lastname: Giller
authors.forename: Iris
authors.initials: I
authors.lastname: Ohmert
authors.forename: Marie-France
authors.initials: MF
authors.lastname: Martin-Eauclaire
authors.forename: Dirk
authors.initials: D
authors.lastname: Trauner
authors.forename: Stefan
authors.initials: S
authors.lastname: Becker
authors.forename: Olaf
authors.initials: O
authors.lastname: Pongs
authors.forename: Marc
authors.initials: M
authors.lastname: Baldus
mesh_terms: D001426:Bacterial Proteins; D002462:Cell Membrane; D006863:Hydrogen-Ion Concentration; D051664:Kv1.3 Potassium Channel / Q000737:chemistry* / Q000502:physiology; D008081:Liposomes; D009682:Magnetic Resonance Spectroscopy; D008823:Micelles; D018408:Patch-Clamp Techniques; D011166:Porphyrins / Q000494:pharmacology; D024642:Potassium Channels, Voltage-Gated / Q000737:chemistry / Q000502:physiology; D011487:Protein Conformation
chemical_list: D001426:Bacterial Proteins; D051664:Kv1.3 Potassium Channel; D008081:Liposomes; D008823:Micelles; D011166:Porphyrins; D024642:Potassium Channels, Voltage-Gated; C409084:tetraphenylporphyrin