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Selective regulation of human TRAAK channels by biologically active phospholipids.
- Source :
-
Nature chemical biology [Nat Chem Biol] 2021 Jan; Vol. 17 (1), pp. 89-95. Date of Electronic Publication: 2020 Sep 28. - Publication Year :
- 2021
-
Abstract
- TRAAK is an ion channel from the two-pore domain potassium (K <subscript>2P</subscript> ) channel family with roles in maintaining the resting membrane potential and fast action potential conduction. Regulated by a wide range of physical and chemical stimuli, the affinity and selectivity of K <subscript>2P</subscript> 4.1 toward lipids remains poorly understood. Here we show the two isoforms of K <subscript>2P</subscript> 4.1 have distinct binding preferences for lipids dependent on acyl chain length and position on the glycerol backbone. The channel can also discriminate the fatty acid linkage at the SN <subscript>1</subscript> position. Of the 33 lipids interrogated using native mass spectrometry, phosphatidic acid had the lowest equilibrium dissociation constants for both isoforms of K <subscript>2P</subscript> 4.1. Liposome potassium flux assays with K <subscript>2P</subscript> 4.1 reconstituted in defined lipid environments show that those containing phosphatidic acid activate the channel in a dose-dependent fashion. Our results begin to define the molecular requirements for the specific binding of lipids to K <subscript>2P</subscript> 4.1.
- Subjects :
- Adenosine analogs & derivatives
Adenosine chemistry
Adenosine metabolism
Cations, Monovalent
Cloning, Molecular
Gene Expression
Genetic Vectors chemistry
Genetic Vectors metabolism
Glycerophospholipids chemistry
Glycerophospholipids metabolism
Humans
Ion Channel Gating
Ion Transport
Kinetics
Liposomes chemistry
Liposomes metabolism
Phosphatidic Acids metabolism
Phosphatidylcholines chemistry
Phosphatidylcholines metabolism
Phosphatidylethanolamines chemistry
Phosphatidylethanolamines metabolism
Phosphatidylglycerols chemistry
Phosphatidylglycerols metabolism
Phosphatidylserines chemistry
Phosphatidylserines metabolism
Pichia genetics
Pichia metabolism
Potassium metabolism
Potassium Channels genetics
Potassium Channels metabolism
Protein Binding
Protein Isoforms chemistry
Protein Isoforms genetics
Protein Isoforms metabolism
Recombinant Proteins chemistry
Recombinant Proteins genetics
Recombinant Proteins metabolism
Phosphatidic Acids chemistry
Potassium chemistry
Potassium Channels chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 1552-4469
- Volume :
- 17
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Nature chemical biology
- Publication Type :
- Academic Journal
- Accession number :
- 32989299
- Full Text :
- https://doi.org/10.1038/s41589-020-00659-5