Water Accelerates in the Hydration Shell of the N- and C-Terminal Domains of α-Synuclein in the Presence of NaCl.
Water Accelerates in the Hydration Shell of the N- and C-Terminal Domains of α-Synuclein in the Presence of NaCl.
Where did the research take place?
The study site has not been established. Author addresses may differ from where the research occurred.
Blacksburg, US · Author affiliation
Department of Chemistry, Virginia Tech, Blacksburg, Virginia 24061, United States.Location evidence
A plain-language reading has not been prepared for this paper yet.
Original abstract
α-Synuclein (α-Syn) is an intrinsically disordered protein (IDP) whose aggregation into fibrils is implicated in Parkinson's disease (PD). While benign α-Syn aggregation frequently occurs, off-target aggregates are implicated in disease progression. Although most mechanisms of toxic α-Syn aggregate formation are unknown, high concentrations of salt ions have been shown to systematically result in faster aggregation. Previous work suggests that salt slows water in the hydration shell of α-Syn, promoting intermolecular interactions. Here, we use polarizable molecular dynamics (MD) to investigate the interactions between α-Syn and water in response to an increased NaCl concentration. While we also find that the water in the hydration shell of the nonamyloid-β component (NAC) domain slows down with increasing salt concentration, the water in the hydration shell of the N- and C-terminal domains accelerates. The segments of the N- and C-terminal domains that show faster water diffusion kinetics corroborate with truncation experiment results. Overall, our work suggests that α-Syn aggregation is related to partial salt-induced dehydration of the N- and C-terminal domains.