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

ABSTRACT: The effect of an amyloidogenic intrinsically disordered protein, ?-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 ?-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, ?-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.

SUBMITTER: Mukherjee SK 

PROVIDER: S-EPMC7496936 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature