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Assessing the phospholipid lateral reorganization in a bilayer upon α-Synuclein binding

Monday, October 24, 2011 — Poster Session I

Noon – 2:00 p.m.

Natcher Conference Center




  • Z Jiang
  • JC Lee


α-Synuclein (α-syn) is an abundant protein of ill-defined function enriched in the presynaptic terminals of neurons. The presence of amyloid α-syn in the brain is a hallmark of Parkinson's disease and its conformation and aggregation kinetics are intimately tied to membranes. While much research efforts have been geared towards the protein conformational dynamics upon membrane interaction, a central question that remains to be addressed is how the protein association influences the phospholipid bilayer structure and properties. Particularly, we sought to examine lateral reorganization processes of the phospholipids by using a fluorescence assay in which we measure fluorophore-labeled phospholipid (NBD-PA) self-quenching in large unilamellar vesicles (LUVs,~100nm). We performed titrations of α-syn into a series of LUVs containing ~50% anionic lipids (PA,PS and PI, respectively) incorporated with a small amount of NBD-PA (0.2%) and found that in all cases, the protein laterally sequesters PA upon membrane binding, suggesting perturbation of the bilayer. Our results also showed that α-syn has preferences for PI and PA compared to PS. To gain further insights, we will employ fluorescence correlation spectroscopy to evaluate the lateral diffusion times of specific phospholipids as well as to characterize the bilayer morphology by fluorescence microscopic studies of giant unilamellar vesicles.

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