title: Identification of novel cholesterol-binding regions in Kir2 channels.
abstract: Inwardly rectifying potassium (Kir) channels play an important role in setting the resting membrane potential and modulating membrane excitability. We have recently shown that cholesterol regulates representative members of the Kir family and that in the majority of the cases, cholesterol suppresses channel function. Furthermore, recent data indicate that cholesterol regulates Kir channels by specific sterol-protein interactions, yet the location of the cholesterol binding site in Kir channels is unknown. Using a combined computational-experimental approach, we show that cholesterol may bind to two nonanular hydrophobic regions in the transmembrane domain of Kir2.1 located between adjacent subunits of the channel. The location of the binding regions suggests that cholesterol modulates channel function by affecting the hinging motion at the center of the pore-lining transmembrane helix that underlies channel gating either directly or through the interface between the N and C termini of the channel.
authors.affiliation: From the Department of Medicine, Pulmonary Section, University of Illinois, Chicago, Illinois 60612.
authors.forename: Avia
authors.initials: A
authors.lastname: Rosenhouse-Dantsker
authors.forename: Sergei
authors.initials: S
authors.lastname: Noskov
authors.forename: Serdar
authors.initials: S
authors.lastname: Durdagi
authors.forename: Diomedes E
authors.initials: DE
authors.lastname: Logothetis
authors.forename: Irena
authors.initials: I
authors.lastname: Levitan
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D002784:Cholesterol / Q000737:chemistry* / Q000378:metabolism; D057927:Hydrophobic and Hydrophilic Interactions; D062105:Molecular Docking Simulation; D009865:Oocytes; D024661:Potassium Channels, Inwardly Rectifying / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D014982:Xenopus laevis
chemical_list: C489461:Kir2.1 channel; D024661:Potassium Channels, Inwardly Rectifying; D002784:Cholesterol
keywords: Cholesterol; Ion Channels; Kir Channels; Lipids; Membrane Lipids; Potassium Channels
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