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

Abstract Cytotoxicity of A β with redox active metals in neuronal cells has been implicated in the progression of Alzheimer's disease (AD). Zn 7 MT-3 protects cell against A β –Cu 2+ toxicity. The roles of single domain proteins ( α / β ) and α – β domain–domain interaction of Zn 7 MT-3 in its anti-A β 1–42 –Cu 2+ toxicity activity were investigated herein. A β 1–42 and four mutants of human MT3 ( α / β domain, β (MT3)– α (MT1) and Δ31–34) were prepared and characterized. A β 1–42 –Cu 2+ 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.