Phosphoinositide-mediated gating of inwardly rectifying K(+) channels.
Phosphoinositides, such as phosphatidylinositol-bisphosphate (PIP(2)), control the activity of many ion channels in yet undefined ways. Inwardly, rectifying potassium (Kir) channels were the first shown to be dependent on direct interactions with phosphoinositides. Alterations in channel-PIP(2) interactions affect Kir single-channel gating behavior. Aberrations in channel-PIP(2) interactions can lead to human disease. As the activity of all Kir channels depends on their interactions with phosphoinositides, future research will aim to understand the molecular events that occur from phosphoinositide binding to channel gating. The determination of atomic resolution structures for several mammalian and bacterial Kir channels provides great promise towards this goal. We have mapped onto the three-dimensional channel structure the position of basic residues identified through mutagenesis studies that contribute to the sensitivity of a Kir channel to PIP(2). The localization of these putative PIP(2)-interacting residues relative to the channel's permeation pathway has given rise to a testable model, which could account for channel activation by PIP(2).
Logothetis
Diomedes E
DE
Department of Structural and Chemical Biology, Mount Sinai School of Medicine, New York, NY, 10029, USA. diomedes.logothetis@mssm.edu
Jin
Taihao
T
Lupyan
Dmitry
D
Rosenhouse-Dantsker
Avia
A
D000595:Amino Acid Sequence; D000818:Animals; D006801:Humans; D015640:Ion Channel Gating / Q000502:physiology*; D008969:Molecular Sequence Data; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000502:physiology; D010716:Phosphatidylinositols / Q000502:physiology*; D024661:Potassium Channels, Inwardly Rectifying / Q000145:classification / Q000235:genetics / Q000502:physiology*
D019269:Phosphatidylinositol 4,5-Diphosphate; D010716:Phosphatidylinositols; D024661:Potassium Channels, Inwardly Rectifying