Fezoua-Boubegtiten, Zahia; Desbat, Bernard; Brisson, Alain; Gounou, Celine; Laguerre, Michel; Lecomte, Sophie
Effect of Mg2+ versus Ca2+ on the behavior of Annexin A5 in a membrane-bound state
EUROPEAN BIOPHYSICS JOURNAL WITH BIOPHYSICS LETTERS, 40:641-649, MAY 2011

Annexin A5 (AnxA5) binds to negatively charged phospholipid membranes in a Ca2+ dependent manner. Several studies already demonstrate that Mg2+ ions cannot induce the binding. In this paper, quartz crystal microbalance with dissipation monitoring (QCM-D), Brewster angle microscopy (BAM), polarization modulation infrared reflection absorption spectroscopy (PMIRRAS) and molecular dynamics (MD) were performed to elucidate the high specificity of Ca2+ versus Mg2+ on AnxA5 binding to membrane models. In the presence of Ca2+, AnxA5 showed a strong interaction with lipids, the protein is adsorbed mainly in alpha-helix under the DMPS monolayer, with an orientation of the alpha-helices axes slightly tilted with respect to the normal of the phospholipid monolayer as revealed by PMIRRAS. The Ca2+ ions interact strongly with the phosphate group of the phospholipid monolayer. In the presence of Mg2+, instead of Ca2+, no interaction of AnxA5 with lipids was detected. Molecular dynamics simulations allow us to explain the high specificity of calcium. Ca2+ ions are well exposed and surrounded by labile water molecules at the surface of the protein, which then favour their binding to the phosphate group of the membrane, explaining their specificity. To the contrary, Mg2+ ions are embedded in the protein structure, with a smaller number of water molecules strongly bound. We conclude that the embedded Mg2+ ions inside the AnxA5 structure are not able to link the protein to the phosphate group of the phospholipids for this reason.

DOI:10.1007/s00249-010-0665-0

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