A molecular switch controls the impact of cholesterol on a Kir channel

• DOI: 10.1073/pnas.2109431119
• Publication Date: 2022-03-25T18:14:07Z
• Authors: Valentina Corradi; Anna N. Bukiya; Williams E. Miranda; Meng Cui; Leigh D. Plant; Diomedes E. Logot...; D. Peter Tieleman; Sergei Y. Noskov; Avia Rosenhouse-D...
• Keywords: 0303 health sciences; 03 medical and health sciences; Cholesterol; G Protein-Coupled Inwardly-Rectifying Potassium Channels; Cell Membrane; Potassium; Biological Sciences; Signal Transduction

Significance Cholesterol 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.