Copper-assisted interaction between amyloid-? and prion: Ternary metal complexes with A? N-terminus and octarepeat

Alzheimer and prion diseases are neurodegenerative disorders in which amyloid-beta (A?) and prion protein (PrP), respectively, failed their normal functions inducing cellular apoptosis. Histidine-based highaffinity metal-binding sites in the N-terminus domains, which favor the binding of transition metals such as copper and zinc, feature both A? and PrP. Recently, the biological role of copper(II) on the two protein interaction has been revealed. Many studies have been focused on copper(II) binding affinity for both A? or prion protein while ternary complexes formed by this metal with both proteins have not been investigated. Here we report a combined ESI MS, potentiometric and spectroscopic (CD, UV-Vis) study on ternary complexes formed by copper(II) ion with A? and PrP peptides fragments containing potential metal binding sites. In particular, A?(1-4), A?(1-6), Ac-A?(1-6), A?(1-16)PEG and the octarepeat (PHGGGWGQ) of prion protein were studied. ESI-MS results indicate that the formation of 1:1:1 ternary complexes occurred at the physiological pH range. Potentiometric and spectroscopic data demonstrate that in a large pH range, ternary species prevail over binary species with the histidine-driven amide deprotonation.