Structural Modulation of Alpha-Synuclein by DNA Aptamers

Alpha-synuclein (α-syn) is an intrinsically disordered presynaptic protein involved in neurodegenerative diseases such as Parkinson’s disease, largely due to its ability to form pathological aggregates. This project aims to investigate how specific DNA aptamers modulate the structural ensemble of α-syn in solution using Small-Angle X-Ray Scattering (SAXS) at the BM29 beamline at ESRF. Aptamers are short oligonucleotides known to bind α-syn with high specificity and inhibit its aggregation, potentially stabilizing non-toxic conformations. SAXS experiments will be performed across a temperature range of 5–40 °C to assess changes in flexibility and global conformation of α-syn in the presence and absence of aptamers. Data will be analyzed using Ensemble Optimization Methods (EOM) to capture conformational heterogeneity. This study seeks to provide structural insight into aptamer-induced modulation of α-syn and support the development of aptamer-based therapeutics.