Probing Conformational Changes during the Gating Cycle of a Potassium Channel in Lipid Bilayers.
Biophys J
; 112(1): 99-108, 2017 Jan 10.
Article
en En
| MEDLINE
| ID: mdl-28076820
ABSTRACT
Ion conduction across the cellular membrane requires the simultaneous opening of activation and inactivation gates of the K+ channel pore. The bacterial KcsA channel has served as a powerful system for dissecting the structural changes that are related to four major functional states associated with K+ gating. Yet, the direct observation of the full gating cycle of KcsA has remained structurally elusive, and crystal structures mimicking these gating events require mutations in or stabilization of functionally relevant channel segments. Here, we found that changes in lipid composition strongly increased the KcsA open probability. This enabled us to probe all four major gating states in native-like membranes by combining electrophysiological and solid-state NMR experiments. In contrast to previous crystallographic views, we found that the selectivity filter and turret region, coupled to the surrounding bilayer, were actively involved in channel gating. The increase in overall steady-state open probability was accompanied by a reduction in activation-gate opening, underscoring the important role of the surrounding lipid bilayer in the delicate conformational coupling of the inactivation and activation gates.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Proteínas Bacterianas
/
Canales de Potasio
/
Activación del Canal Iónico
/
Membrana Dobles de Lípidos
Idioma:
En
Revista:
Biophys J
Año:
2017
Tipo del documento:
Article
País de afiliación:
Países Bajos