Cupric Ions Selectively Modulate TRAAK-Phosphatidylserine Interactions.

ABSTRACT: TRAAK and TREK2 are two-pore domain K⁺ (K2P) channels and are modulated by diverse factors including temperature, membrane stretching, and lipids, such as phosphatidic acid. In addition, copper and zinc, both of which are essential for life, are known to regulate TREK2 and a number of other ion channels. However, the role of ions in the association of lipids with integral membrane proteins is poorly understood. Here, we discover cupric ions selectively modulate the binding of phosphatidylserine (PS) to TRAAK but not TREK2. Other divalent cations (Ca²⁺, Mg²⁺, and Zn²⁺) bind both channels but have no impact on binding PS and other lipids. Additionally, TRAAK binds more avidly to Cu²⁺ and Zn²⁺ than TREK2. In the presence of Cu²⁺, TRAAK binds similarly to PS with different acyl chains, indicating a crucial role of the serine headgroup in coordinating Cu²⁺. High-resolution native mass spectrometry (MS) enables the determination of equilibrium binding constants for distinct Cu²⁺-bound stoichiometries and uncovered the highest coupling factor corresponds to a 1:1 PS-to-Cu²⁺ ratio. Interestingly, the next three highest coupling factors had a ∼1.5:1 PS-to-Cu²⁺ ratio. Our findings bring forth the role of cupric ions as an essential cofactor in selective TRAAK-PS interactions.

SUBMITTER: Zhu Y 

PROVIDER: S-EPMC9136672 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature