State-of-the-art of metallothioneins at the beginning of the 21st century

Metallothioneins (MTs) are a particular type of small metalloprotein that possess a significant amount of Cys residues, which confer upon them an extraordinary capacity for heavy metal binding. Now, more than 50 years after their discovery and after the publication of thousands of papers, it is generally agreed that they are involved in different biological functions depending on the organisms and/or isoforms considered. This review attempts to critically review the state-of-the-art of these unusual metal-binding proteins. Special attention is devoted to their chemical and structural characterization and reactivity, including a detailed overview of the most prominent techniques used for purification and quantification of MTs, as well as a section with a comparative description of all the three-dimensional structures so far known. Equally important are the biological aspects of MTs, which have also been extensively analyzed. Thus, their in vivo origin, localization and induction pathways, as well as their proposed biological significance is discussed. Finally, the most recent applications of MTs in the Biomedicine and Biotechnology fields and the future goals that, in our opinion, investigators should aim for in MT research are mentioned in the final sections. (C) 2011 Elsevier B.V. All rights reserved.