NMR studies of lipid regulation of the K+ channel KcsA

The membrane environment, including specific lipid characteristics, plays important roles in the folding, stability, and gating of the prokaryotic potassium channel KcsA. Here we study the effect of membrane composition on the population of various functional states of KcsA. The spectra provide support for the previous observation of copurifying phospholipids with phosphoglycerol headgroups. Additional, exogenously added anionic lipids do not appear to be required to stabilize the open conductive conformation of KcsA, which was previously thought to be the case. On the contrary, NMR-based binding studies indicate that including anionic lipids in proteoliposomes at acidic pH leads to a weaker potassium ion affinity at the selectivity filter. Since K+ ion loss leads to channel inactivation, these results suggest that anionic lipids promote channel inactivation. [Display omitted] •NMR detection of co-purifying phospholipid with physphoglycerol headgroup•Lipids affect the conformational preferences of the KcsA.•KcsA open conductive state is stable in the absence of exogenously added anionic lipids.•KcsA losses K+ affinity at acid pH in liposomes with anionic head groups.