Charge substitution shows that repulsive electrostatic interactions impede the oligomerization of Alzheimer amyloid peptides

Abstract

The strong pH dependence of Aβ oligomerization could arise from favorable intermolecular charge–charge interactions between His and carboxylate groups, or, alternatively, by mutual electrostatic repulsion of peptide molecules. To test between these two possibilities, the pH dependence of the oligomerization of Aβ and three charge substitution variants with Asp, Glu and His substituted by Ala is measured. All four peptides oligomerize, as detected by thioflavin T fluorescence, turbidity, and amyloid fibril formation; therefore, specific charge–charge interactions are nonessential for oligomerization. The strong negative correlation between net charge and oligomerization indicates that electrostatic repulsion between Aβ monomers impedes their association.