Cholesterol regulates prokaryotic Kir channel by direct binding to channel protein

► Channel activity of Kir2 sub-family of inward rectifiers is strongly suppressed by the elevation of cellular cholesterol. ► The goal of this study is to find the mechanism by which cholesterol regulate the function of Kir channels. ► Provides first direct evidence for specific binding between cholesterol and ion channel. ► Cholesterol-Kir binding is required for cholesterol suppression of the channel function. ► There is competition between radioactive and non-radioactive cholesterol for the binding site.