A molecular switch controls the impact of cholesterol on a Kir channel
Valentina Corradi, Anna N. Bukiya, Williams E. Miranda, Meng Cui, Leigh D. Plant, Diomedes E. Logothetis, D. Peter Tieleman, Sergei Y. Noskov, Avia Rosenhouse‐Dantsker
Abstract
SignificanceCholesterol is one of the main components found in plasma membranes and is involved in lipid-dependent signaling enabled by integral membrane proteins such as inwardly rectifying potassium (Kir) channels. Similar to other ion channels, most of the Kir channels are down-regulated by cholesterol. One of the very few notable exceptions is Kir3.4, which is up-regulated by this important lipid. Here, we discovered and characterized a molecular switch that controls the impact (up-regulation vs. down-regulation) of cholesterol on Kir3.4. Our results provide a detailed molecular mechanism of tunable cholesterol regulation of a potassium channel.