The α and β domains of human metallothionein-3 co-operatively protect against Aβ _1-42-Cu ²⁺ cytotoxicity

Cytotoxicity of Aβ with redox active metals in neuronal cells has been implicated in the progression of Alzheimer's disease (AD). Zn ₇MT-3 protects cell against Aβ-Cu ²⁺ toxicity. The roles of single domain proteins (α/β) and α-β domain-domain interaction of Zn ₇MT-3 in its anti-Aβ _1-42-Cu ²⁺ toxicity activity were investigated herein. Aβ _1-42 and four mutants of human MT3 (α/β domain, β (MT3)-α (MT1) and Δ31-34) were prepared and characterized. Aβ _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.