Under normal physiological conditions, alpha-synuclein is an abundant, intrinsically disordered protein primarily localized in the presynaptic terminals of nerve cells in the brain. However, abnormal aggregation and fibrillation of alpha-synuclein is a pathogenic hallmark of many neurodegenerative diseases, most prevalently Parkinson’s disease. While the native function of alpha-synuclein and its role in neurodegenerative disease states are still not well understood, it is known that the protein interacts with anionic lipid vesicles through the adoption of an amphipathic alpha-helical structure. As a result, alpha-synuclein has been investigated for its potential role in synaptic vesicle trafficking and neurotransmission. Studies have shown that the size and shape of lipid vesicles affect the binding strength and binding mode of alpha synuclein. However, the presence of alpha-synuclein also affects the size and shape of lipid vesicles. The interconnected nature of these responses and the innate deformability of lipid vesicles complicates conclusions related to the role of native lipid vesicle curvature in alpha-synuclein binding, conformational change, and proclivity for fibrillation.   <br/> <br/>In our current work, we have modified the surface chemistry of gold nanospheres to create a series of rigid lipid vesicle mimics with different core sizes (~10 - 100 nm) in order to conduct a controlled investigation into the effect of mimic surface curvature on the binding behavior of alpha-synuclein. In an attempt to disentangle the roles of lipid vesicle deformability and surface curvature on protein behavior, characterization of the protein-mimic interaction by various techniques including dynamic light scattering, far-UV circular dichroism and a partial enzymatic digest followed by mass spectrometry proteomic analysis will be discussed.

Interaction of alpha-synuclein with rigid lipid vesicle mimics of varying surface curvature

ACS Spring Meeting 2021

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.