Open AccessA molecular switch controls the impact of cholesterol on a Kir channel
Author(s) -
Valentina Corradi,
An. Bukiya,
Williams E. Miranda,
Meng Cui,
Leigh D. Plant,
Diomedes E. Logothetis,
D. Peter Tieleman,
Sergei Y. Noskov,
Avia RosenhouseDantsker
Publication year - 2022
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2109431119
Subject(s) - potassium channel , cholesterol , ion channel , chemistry , inward rectifier potassium ion channel , membrane , microbiology and biotechnology , biophysics , biochemistry , biology , receptor
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.