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Alpha-synuclein selectively binds to anionic phospholipids embedded in liquid-disordered domains

Item Type:Article
Title:Alpha-synuclein selectively binds to anionic phospholipids embedded in liquid-disordered domains
Creators Name:Stoeckl, M. and Fischer, P. and Wanker, E.E. and Herrmann, A.
Abstract:Previous studies indicate that binding of alpha-synuclein to membranes is critical for its physiological function and the development of Parkinson's disease (PD). Here, we have investigated the association of fluorescence-labeled alpha-synuclein variants with different types of giant unilamellar vesicles using confocal microscopy. We found that alpha-synuclein binds with high affinity to anionic phospholipids, when they are embedded in a liquid-disordered as opposed to a liquid-ordered environment. This indicates that not only electrostatic forces but also lipid packing and hydrophobic interactions are critical for the association of alpha-synuclein with membranes in vitro. When compared to wild-type alpha-synuclein, the disease-causing alpha-synuclein variant A30P bound less efficiently to anionic phospholipids, while the variant E46K showed enhanced binding. This suggests that the natural association of alpha-synuclein with membranes is altered in the inherited forms of Parkinson's disease.
Keywords:Lipid Domains, Greek Small Letter Alpha-Synuclein, Mutants, Giant Unilamellar Vesicles, Fluorescence Microscopy
Source:Journal of Molecular Biology
Page Range:1394-1404
Date:1 February 2008
Official Publication:https://doi.org/10.1016/j.jmb.2007.11.051
PubMed:View item in PubMed

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