Post-translational modifications can have differing effects that can change the structural or functional properties of proteins. The O-GlcNAc modification in particular is a type of unique dynamic monosaccharide glycosylation that can occur on serine or threonine residues on intracellular proteins. One such protein that is α-synuclein. α-synuclein is a 140 amino acid long protein that has the potential to form amyloid fibers in patients of Parkinson’s Disease. α-synuclein amyloids can form several different strains, or “polymorphs” with different structural features. While all α-synuclein fibers do share canonical in-parallel, in-register amyloid β-sheets, the overall organization and specific residues involved can greatly vary. A current hypothesis on the formation of these polymorphs is that PTMs can force the amyloid fiber into specific structures. O-GlcNAcylation has been extensively studied and can affect the formation of these fibers by significantly impacting the stability, aggregation propensity and toxicity in vivo<i>.</i> Since O-GlcNAcylation does not completely prevent the formation of the amyloid fibers, it is important to understand how the structure of the fibers are changed from typical amyloids and identify the different strains or “polymorphs” of the α-synuclein fibers. Here I will present work demonstrating the differences in aggregation rates and propensities of α-synuclein.

Investigating o-linked glycosylation as a possible inhibitor of α-synuclein amyloid fiber stability

ACS Spring 2022

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