Phosphatidylserine Reversibly Binds Cu²⁺ with Extremely High Affinity

Abstract

Phosphatidylserine (PS) embedded within supported lipid bilayers (SLBs) 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 values pH (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.

Plasma membrane architecture protects Candida albicans from killing by copper

“…The increased sensitivity to papuamide indicated that PS was inappropriately exposed on the plasma membrane surface. Previous studies demonstrated that PS binds copper with very high affinity, and that this interaction can promote membrane damage that could lead to permeability [43, 44, 62]. To test the role of PS, we deleted the CHO1 gene that encodes PS synthase [63].…”

“…Copper binds strongly to membranes, which suggested it could have a direct effect on lipids. In particular, copper binds to PS with picomolar affinity and to PE with micromolar affinity [43, 44]. Copper is thought to bind PS with such high affinity relative to other divalent metals because it can interact in a special configuration with two molecules of PS [42–44].…”

Apoptosis Evaluation by Electrochemical Techniques

“…Recent studies also found that Cu 2+ was able to form a 1:2 complex with PS reversibly with extremely high affinity . The equilibrium dissociation constant was in the femtomolar range.…”

Anomalous behavior of membrane fluidity caused by copper-copper bond coupled phospholipids

“…This can explain the impact of divalent metal ions on membrane fluidity more than that of monovalent ones but cannot be applied to the differences of the influences of divalent ions, such as Ca 2+ , Mg 2+ , Zn 2+ and Cu 2+ . Recently, Cremer and his coworkers studied effects of the Cu 2+ ion on a bilayer comprised of both phosphatidylcholine (PC) and phosphatidylserine (PS), and proposed that the ion was specifically bound to PS 20 . Meanwhile, this binding was only stable under basic conditions, but not at acidic pH values.…”