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

Valentina Corradi | Zendy; An. Bukiya | Zendy; Williams E. Miranda | Zendy; Meng Cui | Zendy; Leigh D. Plant | Zendy; Diomedes E. Logothetis | Zendy; D. Peter Tieleman | Zendy; Sergei Y. Noskov | Zendy; Avia RosenhouseDantsker | Zendy

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A 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

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 , chemistry , ion channel , inward rectifier potassium ion channel , membrane , microbiology and biotechnology , biophysics , mechanism (biology) , biochemistry , biology , receptor , philosophy , epistemology

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.

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