Molecular interactions between silver ions (Ag+) and amyloid-β (Aβ) peptides: binding affinities and structural effects

Abstract

Because silver is toxic to microbes, but not considered toxic to humans, the metal has been used as an antimicrobial agent since ancient times. Today, silver nanoparticles and colloidal silver are used for antibacterial purposes, and silver-peptide and similar complexes are being developed as therapeutic agents. Yet, the health effects of silver exposure are not fully understood, nor are the molecular details of silver-protein interactions. In Alzheimer’s disease (AD), the most common form of dementia worldwide, amyloid-β (Aβ) peptides aggregate to form soluble oligomers that are neurotoxic. Here, we report that monovalent silver ions (Ag+) bind wildtype Aβ40 peptides with a binding affinity of 25 ± 12 µM in MES buffer at 20 °C. The N-terminal His residues are involved as binding ligands. Weaker Ag+ binding is observed for the truncated Aβ(4-40) variant, for an Aβ40 mutant without histidines, and for the wt Aβ40 peptide at acidic pH. Because the Ag+ ions do not induce any changes in the size or structure of Aβ42 oligomers, we speculate that Ag+ ions have a minor influence on Aβ toxicity.