The effect of Cu2+ on a-synuclein (AS) aggregation is important because clinical studies of patients with Parkinson's disease have shown elevated levels of Cu2+ in the cerebrospinal fluid. So far, the molecular architectures of Cu2+- AS fibril complexes at atomic resolution are unknown. The current work identifies for the first time that His50 cannot bind Cu2+ ions in mature fibrils. Moreover, it shows hopping of Cu2+ ions between residues in AS fibrils and changes in the Cu2+ coordination mode in Cu2+ ions that bind in the termini of AS. The current study combines extensive experimental techniques, density functional theory calculations, and computational modeling tools to provide a complete description of the Cu2+ binding site in AS fibrils. Our findings illustrate for the first time the specific interactions between Cu2+ ions and AS fibrils, suggesting a new mechanistic perspective on the effect of Cu2+ ions on AS aggregation.
|Titolo:||Fibrils of α-Synuclein Abolish the Affinity of Cu2+-Binding Site to His50 and Induce Hopping of Cu2+ Ions in the Termini|
|Citazione:||Bloch, D.N., Kolkowska, P., Tessari, I., Baratto, M.C., Sinicropi, A., Bubacco, L., et al. (2019). Fibrils of α-Synuclein Abolish the Affinity of Cu2+-Binding Site to His50 and Induce Hopping of Cu2+ Ions in the Termini. INORGANIC CHEMISTRY, 58(16), 10920-10927.|
|Appare nelle tipologie:||1.1 Articolo in rivista|