Metal ions affect the formation and stability of amyloid aggregates at multiple length scales

초록

Amyloid beta (A beta) aggregates, which are a hallmark for neurodegenerative disease, are formed through a self-assembly process such as aggregation of A beta peptide chains. This aggregation process depends on the solvent conditions under which the proteins are aggregated. Nevertheless, the underlying mechanism of the ionic effect on the formation and stability of amyloid aggregates has not been fully understood. Here, we report how metal ions play a role in the formation and stability of A beta aggregates at different length scales, i.e. oligomers and fibrils. It is shown that the metal (i.e. zinc or copper) ion increases the stability of A beta oligomers, whereas the metal ion reduces the stability of A fibrils. In addition, we found that zinc ions are able to more effectively destabilize fibril structures than copper ions. Metal ion-mediated (de)stabilization of A beta oligomers (or fibrils) is attributed to the critical effect of the metal ion on the beta-sheet rich crystalline structure of the amyloid aggregate and the status of hydrogen bonds within the aggregate. Our study sheds light on the role of the metal ion in stabilizing the amyloid oligomers known as a toxic agent (to functional cells), which is consistent with clinical observation that high concentrations of metal ions are found in patients suffering from neurodegenerative diseases.

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