Updating of metallothioneins: structural characteristics and functions

Metallothioneins (MTs), firstly isolated in the equine kidney, are ubiquitous low molecular weight proteins and polypeptides of extremely high metal and cysteine content which give rise to metal-thiolate clusters. Any protein or polypeptide resembling mammalian MTs can be classified as MT. MTs constitute a protein superfamily of 15 families which comprise a large number of sequences inferred from both aminoacid and polynucleotide sequences obtained from all animal phyla examined so far and also from certain fungi, plants and cyanobacteria. In mammals, the MT gene family consists of four subfamilies designated MT-1 through MT-4. The study of MTs needs the competences in different fields, which range from analytical chemistry and structural spectroscopy to molecular biology and medicine. Till now does not exist a simple quantification method whereas the sophisticated 2D NMR spectroscopy shows that notwithstanding MTs have different aminoacid sequences they have similar spatial structure with metal-thiolate clusters containing 3 or 4 bivalent metal ions. Increasing body of evidence shows that mammalian MT-1 / MT-2 isoforms are involved in zinc homeostasis, protection against heavy metal toxicity and oxidative stress. MT-3 is expressed mainly in neurons but also in glia while MT-4 is mostly present in differentiating stratified squamous epithelial cells. Due to the induction by a variety of different stimuli the MT determination is considered a valid biomarker in environmental and medical field. However the true biological role of these proteins is still enigmatic.