M35 oxidation induces Abeta40-like structural and dynamical changes in Abeta42.

Oxidizing a single M35 residue of Abeta leads to delayed aggregation and reduced toxicity. To understand the molecular mechanism of this effect, we examined the structural and dynamical consequences of M35 oxidation. We found the mobility of the C-terminal residues of Abeta42 is greatly enhanced upon M35 oxidation. In contrast, methyl groups in the central hydrophobic cluster become less flexible. Taken together, we conclude that Abeta42ox undergoes Abeta40-like structural and dynamical changes, which contribute to its reduced aggregation and toxicity.