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Selective regulation of human TRAAK channels by biologically active phospholipids.

Authors :
Schrecke S
Zhu Y
McCabe JW
Bartz M
Packianathan C
Zhao M
Zhou M
Russell D
Laganowsky A
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.

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