The α and β domains of human metallothionein-3 co-operatively protect against Aβ1–42–Cu2+ cytotoxicity

Cytotoxicity of Aβ with redox active metals in neuronal cells has been implicated in the progression of Alzheimer's disease (AD). Zn7MT-3 protects cell against Aβ–Cu2+ toxicity. The roles of single domain proteins (α/β) and α–β domain–domain interaction of Zn7MT-3 in its anti-Aβ1–42–Cu2+ toxicity activity were investigated herein. Aβ1–42 and four mutants of human MT3 (α/β domain, β (MT3)–α (MT1) and Δ31–34) were prepared and characterized. Aβ1–42–Cu2+ induced hydroxyl radical and ROS production with/without Zn-MTs were measured by fluorescence spectroscopy and DCFH-DA in living cells, respectively. These results indicate that the two domains form a co-operative unit and each of them is indispensable in conducting its bioactivity.