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bioRxiv · 10.1101/2021.01.15.426884

Phospholipids Uniquely Modify Secondary Structure of α-Synuclein Oligomers

Dou, T.·Zhou, L.·Kurouski, D.
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Abstract

Parkinson disease (PD) is a severe neurological disorder that affects more than a million people in the U.S. alone. A hallmark of PD is the formation of intracellular -synuclein (-Syn) protein aggregates called Lewy bodies (LBs). Although this protein does not have a particular localization in the central neural system, -Syn aggregates are primarily found in certain areas of midbrain, hypothalamus and thalamus. Microscopic analysis of LBs revealed fragments of lipid-rich membranes, organelles and vesicles. These and other pieces of experimental evidence suggest -Syn aggregation can be triggered by lipids. In this study, we used atomic force microscope Infrared (AFM-IR) spectroscopy to investigate structural organization of individual -Syn oligomers grown in the presence of two different phospholipids vesicles. AFM-IR is a modern optical nanoscopy technique that has single-molecule sensitivity and sub-diffraction spatial resolution. Our results show that -Syn oligomers grown in the presence of phosphatidylcholine have distinctly different structure than oligomers grown in the presence on phosphatidylserine. We infer that this occurs because of specific charges adopted by lipids, which in turn governs protein aggregation. We also found that protein to phospholipid ratio makes a substantial impact on the structure of -Syn oligomers. These findings demonstrate that -Syn is far more complex than expected from the perspective of structural organization of oligomeric species.

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Dou, T., Zhou, L., Kurouski, D.. 2021-01-17. Phospholipids Uniquely Modify Secondary Structure of α-Synuclein Oligomers. https://doi.org/10.1101/2021.01.15.426884

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