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α-Synuclein oligomers with broken helical conformation form lipoprotein nanoparticles.

The Journal of biological chemistry (2013-04-24)
Jobin Varkey, Naoko Mizuno, Balachandra G Hegde, Naiqian Cheng, Alasdair C Steven, Ralf Langen
RÉSUMÉ

α-Synuclein (αS) is a membrane-binding protein with sequence similarity to apolipoproteins and other lipid-carrying proteins, which are capable of forming lipid-containing nanoparticles, sometimes referred to as "discs." Previously, it has been unclear whether αS also possesses this property. Using cryo-electron microscopy and light scattering, we found that αS can remodel phosphatidylglycerol vesicles into nanoparticles whose shape (ellipsoidal) and dimensions (in the 7-10-nm range) resemble those formed by apolipoproteins. The molar ratio of αS to lipid in nanoparticles is ∼1:20, and αS is oligomeric (including trimers and tetramers). Similar nanoparticles form when αS is added to vesicles of mitochondrial lipids. This observation suggests a mechanism for the previously reported disruption of mitochondrial membranes by αS. Circular dichroism and four-pulse double electron electron resonance experiments revealed that in nanoparticles αS assumes a broken helical conformation distinct from the extended helical conformation adopted when αS is bound to intact vesicles or membrane tubules. We also observed αS-dependent tubule and nanoparticle formation in the presence of oleic acid, implying that αS can interact with fatty acids and lipids in a similar manner. αS-related nanoparticles might play a role in lipid and fatty acid transport functions previously attributed to this protein.

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Sigma-Aldrich
2-Oleoyl-1-palmitoyl-sn-glycero-3-phosphocholine, ≥99.0% (TLC)
Sigma-Aldrich
2-Oleoyl-1-palmitoyl-sn-glycero-3-phosphocholine, ≥95.5% (GC), ≥98% (TLC)