A structural link between inactivation and block of a K+ channel.
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.
Ader
Christian
C
Max-Planck Institute for Biophysical Chemistry, Department of NMR-Based Structural Biology, Am Fassberg 11, 37077 Göttingen, Germany.
Schneider
Robert
R
Hornig
Sönke
S
Velisetty
Phanindra
P
Wilson
Erica M
EM
Lange
Adam
A
Giller
Karin
K
Ohmert
Iris
I
Martin-Eauclaire
Marie-France
MF
Trauner
Dirk
D
Becker
Stefan
S
Pongs
Olaf
O
Baldus
Marc
M
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
D001426:Bacterial Proteins; D051664:Kv1.3 Potassium Channel; D008081:Liposomes; D008823:Micelles; D011166:Porphyrins; D024642:Potassium Channels, Voltage-Gated; C409084:tetraphenylporphyrin