Selective regulation of human TRAAK channels by biologically active phospholipids.

Autor: Schrecke S; Department of Chemistry, Texas A&M University, College Station, TX, USA., Zhu Y; Department of Chemistry, Texas A&M University, College Station, TX, USA., McCabe JW; Department of Chemistry, Texas A&M University, College Station, TX, USA., Bartz M; Department of Chemistry, Texas A&M University, College Station, TX, USA., Packianathan C; Department of Chemistry, Texas A&M University, College Station, TX, USA., Zhao M; Department of Biochemistry and Molecular Biology, The University of Chicago, Chicago, IL, USA., Zhou M; Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX, USA., Russell D; Department of Chemistry, Texas A&M University, College Station, TX, USA., Laganowsky A; Department of Chemistry, Texas A&M University, College Station, TX, USA. alaganowsky@chem.tamu.edu.
Jazyk: angličtina
Zdroj: Nature chemical biology [Nat Chem Biol] 2021 Jan; Vol. 17 (1), pp. 89-95. Date of Electronic Publication: 2020 Sep 28.
DOI: 10.1038/s41589-020-00659-5
Abstrakt: TRAAK is an ion channel from the two-pore domain potassium (K 2P ) 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 2P 4.1 toward lipids remains poorly understood. Here we show the two isoforms of K 2P 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 1 position. Of the 33 lipids interrogated using native mass spectrometry, phosphatidic acid had the lowest equilibrium dissociation constants for both isoforms of K 2P 4.1. Liposome potassium flux assays with K 2P 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 2P 4.1.
Databáze: MEDLINE
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