Metallothionein 3 (MT3) is a member of the metallothionein family, which consists of low-molecular-weight, cysteine-rich proteins. These proteins are known for their ability to bind heavy metals through the thiol groups of their cysteine residues. MT3, in particular, is predominantly found in the brain and has been implicated in various cellular processes and diseases.
MT3 contains three zinc and three copper atoms per polypeptide chain, with a minor amount of cadmium . The human recombinant form of MT3 is produced in E. coli and consists of a single polypeptide chain containing 91 amino acids, with a molecular mass of approximately 9.3 kDa . The recombinant protein is often fused to a His-tag at the N-terminus to facilitate purification.
MT3 plays a crucial role in the regulation of intracellular metal homeostasis. It binds and releases transition metals such as zinc and copper, depending on the cellular environment . This binding capability allows MT3 to participate in various cellular functions, including the regulation of reactive oxygen species (ROS) production and the maintenance of redox balance .
MT3 has been associated with several neurological conditions. For instance, it has been shown to inhibit the survival and neurite formation of cortical neurons in vitro . Abnormal levels of MT3 have been linked to neurodegenerative diseases such as Alzheimer’s disease and ischemic seizures . Additionally, MT3 has been implicated in the development of sorafenib-resistant phenotypes in hepatocellular carcinoma cells, suggesting its role in cancer progression and drug resistance .
The expression of MT3 is regulated by various factors, including metal ions and oxidative stress. The protein’s structure can change depending on the number of bound metals, which in turn affects its functional properties . Understanding these regulatory mechanisms is crucial for elucidating the role of MT3 in health and disease.