Alteration of the Conformational Dynamics of a DNA Hairpin by α-Synuclein in the Presence of Aqueous Two-Phase Systems.

Abstract

The effect of an amyloidogenic intrinsically disordered protein, α‐synuclein, which is associated with Parkinson's disease (PD), on the conformational dynamics of a DNA hairpin (DNA‐HP) was studied by employing the single‐molecule Förster resonance energy transfer method. The open‐to‐closed conformational equilibrium of the DNA‐HP is drastically affected by binding of monomeric α‐synuclein to the loop region of the DNA‐HP. Formation of a protein‐bound intermediate conformation is fostered in the presence of an aqueous two‐phase system mimicking intracellular liquid‐liquid phase separation. Using pressure modulation, additional mechanistic information about the binding complex could be retrieved. Hence, in addition to toxic amyloid formation, α‐synuclein may alter expression profiles of disease‐modifying genes in PD. Furthermore, these findings might also have significant bearings on the understanding of the physiology of organisms thriving at high pressures in the deep sea.