Effect of Mg2+ versus Ca2+ on the behavior of annexin A5 in a membrane-bound state.
Annexin A5 (AnxA5) binds to negatively charged phospholipid membranes in a Ca(2+) dependent manner. Several studies already demonstrate that Mg(2+) 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 Ca(2+) versus Mg(2+) on AnxA5 binding to membrane models. In the presence of Ca(2+), AnxA5 showed a strong interaction with lipids, the protein is adsorbed mainly in α-helix under the DMPS monolayer, with an orientation of the α-helices axes slightly tilted with respect to the normal of the phospholipid monolayer as revealed by PMIRRAS. The Ca(2+) ions interact strongly with the phosphate group of the phospholipid monolayer. In the presence of Mg(2+), instead of Ca(2+), no interaction of AnxA5 with lipids was detected. Molecular dynamics simulations allow us to explain the high specificity of calcium. Ca(2+) 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, Mg(2+) ions are embedded in the protein structure, with a smaller number of water molecules strongly bound. We conclude that the embedded Mg(2+) ions inside the AnxA5 structure are not able to link the protein to the phosphate group of the phospholipids for this reason.
Laboratoire de Chimie et Biologie des Membranes et des Nano-Objets, UMR CBMN, CNRS-Université Bordeaux ENITAB, IECB, Pessac, France.
Zahia
Z
Fezoua-Boubegtiten
Bernard
B
Desbat
Alain
A
Brisson
Céline
C
Gounou
Michel
M
Laguerre
Sophie
S
Lecomte
D000327:Adsorption; D000388:Air; D017304:Annexin A5 / Q000737:chemistry* / Q000378:metabolism*; D002118:Calcium / Q000494:pharmacology*; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism*; D008051:Lipid Bilayers / Q000737:chemistry / Q000378:metabolism; D008274:Magnesium / Q000494:pharmacology*; D056004:Molecular Dynamics Simulation; D011485:Protein Binding / Q000187:drug effects; D011487:Protein Conformation; D014494:Unithiol / Q000737:chemistry / Q000378:metabolism; D014867:Water / Q000737:chemistry
D017304:Annexin A5; D008051:Lipid Bilayers; D014867:Water; D014494:Unithiol; D008274:Magnesium; D002118:Calcium
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