Interactions between fatty acids and alpha -synuclein

doi:10.1194/jlr.M600003-JLR200

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A more recent version of this article appeared on August 1, 2006

Papers In Press, published online ahead of print May 10, 2006
J. Lipid Res., doi:10.1194/jlr.M600003-JLR200

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Submitted on January 3, 2006
Revised on May 3, 2006
Accepted on May 9, 2006

Interactions between fatty acids and $alpha$ -synuclein

Christian Lücke, Donald L. Gantz, Elena Klimtchuk, and James A. Hamilton

NMR, Max Planck Research Unit for Enzymology, Halle 06120

Corresponding Author: luecke{at}enzyme-halle.mpg.de

$alpha$ -Synuclein is an amyloidogenic neuronal protein associated with several neurodegenerative disorders. Although unstructured in solution, $alpha$ -synuclein forms $alpha$ -helices in the presence of negatively-charged lipid surfaces. Moreover, $alpha$ -synuclein was shown to interact with fatty acids (FA) in a manner that promotes protein aggregation. Here, we investigate whether $alpha$ -synuclein has specific FA-binding site(s) similar to fatty acid binding proteins such as the intracellular FABP. Our NMR experiments reveal that FA addition results in (i) simultaneous loss of $alpha$ -synuclein signal in both ¹H and ¹³C spectra and (ii) appearance of a very broad FA ¹³C-carboxyl signal. These data exclude high-affinity binding of FA molecules to specific $alpha$ -synuclein sites, as in FABP. One possible mode of binding was revealed by EM studies of oleic acid bilayers at pH 7.8; these high-molecular-weight FA aggregates possess a net negative surface charge because they contain FA anions, and they were easily disrupted to form smaller particles in the presence of $alpha$ -synuclein, thus indicating a direct protein-lipid interaction. We conclude that $alpha$ -synuclein is not likely to act as an intracellular FA carrier. Binding to negatively-charged membranes, however, appears to be an intrinsic property of $alpha$ -synuclein that is most likely related to its physiological role(s) in the cell.

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Interactions between fatty acids and -synuclein

Interactions between fatty acids and $alpha$ -synuclein