Abstract
Protein aggregation is an important problem for human health and biotechnology, with consequences in areas ranging from neurodegenerative diseases to protein production yields. Methods to modulate protein aggregation are therefore essential. One suggested method to modulate protein aggregation is the use of nucleic acid aptamers, that is, single-stranded nucleic acids that have been selected to specifically bind to a target. Previous studies in some systems have demonstrated that aptamers may inhibit protein aggregation, including for α-synuclein, a protein implicated in synucleinopathies. However, the mechanisms by which aptamers might affect or modulate aggregation have not been fully determined. In this study, we investigated the effect of an aptamer that binds α-synuclein oligomer, T-SO508, on α-synuclein aggregation in vitro using thioflavin T to monitor aggregation kinetics, and we performed atomic force microscopy, transmission electron microscopy, and analytical ultracentrifugation to characterize intermediate structures. The results indicated that T-SO508, but not control DNA sequences, extends the lag phase of aggregation and stabilizes formation of a small non-fibrillar aggregate complex. Attempts to use the aptamer-induced complexes to seed fibril formation did not in fact accelerate aggregation, indicating that these structures are off-pathway for aggregation. This study highlights a potential mechanism by which aptamers may modulate the aggregation properties of proteins.