Phosphatidylserine Reversibly Binds Cu2+ with Extremely High Affinity

• Published in: Journal of the American Chemical Society 2012-05, Vol.134 (18), p.7773-7779
• Main Authors: Monson, Christopher F, Cong, Xiao, Robison, Aaron D, Pace, Hudson P, Liu, Chunming, Poyton, Matthew F, Cremer, Paul S
• Format: Article
• Language: English
• Subjects: Cations, Divalent - metabolism; Copper - metabolism; Hydrogen-Ion Concentration; Kinetics; Lipid Bilayers - metabolism; Microfluidic Analytical Techniques; Phosphatidylserines - metabolism
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja212138e

Phosphatidylserine (PS) embedded within supported lipid bilayers was found to bind Cu2+ from solution with extraordinarily high affinity. In fact, the equilibrium dissociation constant was in the femtomolar range. The resulting complex formed in a 1:2 Cu2+-to-PS ratio and quenches a broad spectrum of lipid-bound fluorophores in a reversible and pH-dependent fashion. At acidic pH values, the fluorophores were almost completely unquenched, while at basic pH values significant quenching (85–90%) was observed. The pH at which the transition occurred was dependent on the PS concentration and ranged from approximately pH 5 to 8. The quenching kinetics was slow at low Cu2+ concentrations and basic pH values (up to several hours), while the unquenching reaction was orders of magnitude more rapid upon lowering the pH. This was consistent with diffusion-limited complex formation at basic pH but rapid dissociation under acidic conditions. The tight binding of Cu2+ to PS may have physiological consequences under certain circumstances.