Probing Conformational Changes during the Gating Cycle of a Potassium Channel in Lipid Bilayers.

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.

journal_name

Biophys J

journal_title

Biophysical journal

authors

van der Cruijsen EA,Prokofyev AV,Pongs O,Baldus M

doi

10.1016/j.bpj.2016.12.001

subject

Has Abstract

pub_date

2017-01-10 00:00:00

pages

99-108

issue

1

eissn

0006-3495

issn

1542-0086

pii

S0006-3495(16)34274-6

journal_volume

112

pub_type

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