Cupric Ions Selectively Modulate TRAAK-Phosphatidylserine Interactions

Area of Science:

• Molecular biology
• Biophysics
• Ion channel research

Background:

• Two-pore domain potassium (K2P) channels like TRAAK and TREK2 are regulated by lipids and ions.
• The influence of metal ions on lipid-protein interactions in ion channels is not well understood.

Purpose of the Study:

• To investigate the role of divalent cations in modulating lipid binding to TRAAK and TREK2 K2P channels.
• To elucidate the specific interactions between cupric ions, lipids, and TRAAK channels.

Main Methods:

• High-resolution native mass spectrometry (MS) was employed to study ion and lipid binding.
• Equilibrium binding constants were determined for various ion-lipid-channel stoichiometries.

Main Results:

• Cupric ions (Cu2+) selectively enhance phosphatidylserine (PS) binding to TRAAK, but not TREK2.
• TRAAK exhibits higher affinity for Cu2+ and Zn2+ compared to TREK2.
• The serine headgroup of PS is crucial for coordinating Cu2+ binding to TRAAK.
• MS revealed distinct Cu2+-bound stoichiometries, with a 1:1 PS-to-Cu2+ ratio showing the highest coupling.

Conclusions:

• Cupric ions act as essential cofactors mediating selective interactions between TRAAK and phosphatidylserine.
• This study provides novel insights into ion-lipid-protein interactions in K2P channels.