What Is the Preferred Conformation of Phosphatidylserine-Copper(II) Complexes? A Combined Theoretical and Experimental Investigation

Kari Kusler, Samuel O. Odoh, Alexey Silakov, Matthew F. Poyton, Saranya Pullanchery, Paul S. Cremer, Laura Gagliardi

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13 Scopus citations


Phosphatidylserine (PS) has previously been found to bind Cu2+ in a ratio of 1 Cu2+ ion per 2 PS lipids to form a complex with an apparent dissociation constant that can be as low as picomolar. While the affinity of Cu2+ for lipid membranes containing PS lipids has been well characterized, the structural details of the Cu-PS2 complex have not yet been reported. Coordinating to one amine and one carboxylate moiety on two separate PS lipids, the Cu-PS2 complex is unique among ion-lipid complexes in its ability to adopt both cis and trans conformations. Herein, we determine which stereoisomer of the Cu-PS2 complex is favored in lipid bilayers using density functional theory calculations and electron paramagnetic resonance experiments. It was determined that a conformation in which the nitrogen centers are cis to each other is the preferred binding geometry. This is in contrast to the complex formed when two glycine molecules bind to Cu2+ in bulk solution, where the cis and trans isomers exist in equilibrium, indicating that the lipid environment has a significant steric effect on the Cu2+ binding conformation. These findings are relevant for understanding lipid oxidation caused by Cu2+ binding to lipid membrane surfaces and will help us understand how ion binding to lipid membranes can affect their physical properties.

Original languageEnglish (US)
Pages (from-to)12883-12889
Number of pages7
JournalJournal of Physical Chemistry B
Issue number50
StatePublished - Dec 22 2016

Bibliographical note

Funding Information:
The computational and theoretical part of this work was supported in part by the U.S. Department of Energy, Office of Basic Energy 1090 Sciences, under SciDAC Grant No. DESC0008666. The experimental lipid chemistry was supported by grants from the National Science Foundation (CHE-1413307) and the Office of Naval Research (N00014-14-1-0792) to P.S.C. The Minnesota Supercomputing Institute provided part of the computational resources for this work.

Publisher Copyright:
© 2016 American Chemical Society.


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