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A molecular switch controls the impact of cholesterol on a Kir channel.
Corradi, Valentina; Bukiya, Anna N; Miranda, Williams E; Cui, Meng; Plant, Leigh D; Logothetis, Diomedes E; Tieleman, D Peter; Noskov, Sergei Y; Rosenhouse-Dantsker, Avia.
Affiliation
  • Corradi V; Centre for Molecular Simulation, University of Calgary, Calgary, AB T2N 1N4, Canada.
  • Bukiya AN; Department of Biological Sciences, University of Calgary, Calgary, AB T2N 1N4, Canada.
  • Miranda WE; Department of Pharmacology, Addiction Science, and Toxicology, The University of Tennessee Health Science Center, Memphis, TN 38163.
  • Cui M; Centre for Molecular Simulation, University of Calgary, Calgary, AB T2N 1N4, Canada.
  • Plant LD; Department of Biological Sciences, University of Calgary, Calgary, AB T2N 1N4, Canada.
  • Logothetis DE; Department of Pharmaceutical Sciences, School of Pharmacy, Bouvé College of Health Sciences, Northeastern University, Boston, MA 02115.
  • Tieleman DP; Department of Pharmaceutical Sciences, School of Pharmacy, Bouvé College of Health Sciences, Northeastern University, Boston, MA 02115.
  • Noskov SY; Department of Pharmaceutical Sciences, School of Pharmacy, Bouvé College of Health Sciences, Northeastern University, Boston, MA 02115.
  • Rosenhouse-Dantsker A; Department of Physiology and Biophysics, Virginia Commonwealth University School of Medicine, Richmond, VA 23298.
Proc Natl Acad Sci U S A ; 119(13): e2109431119, 2022 03 29.
Article in En | MEDLINE | ID: mdl-35333652
ABSTRACT
SignificanceCholesterol 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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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Cholesterol / G Protein-Coupled Inwardly-Rectifying Potassium Channels Language: En Journal: Proc Natl Acad Sci U S A Year: 2022 Document type: Article
Fulltext
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Cholesterol / G Protein-Coupled Inwardly-Rectifying Potassium Channels Language: En Journal: Proc Natl Acad Sci U S A Year: 2022 Document type: Article