Abstract
Metallothioneins (MTs) are a class of ubiquitously occurring low molecular mass, cysteine- and metal-rich proteins containing sulfur-based metal clusters formed with Zn(II), Cd(II), and Cu(I) ions. In mammals, four distinct MT isoforms designated MT-1 through MT-4 exist. The first discovered MT-1/MT-2 are widely expressed isoforms, whose biosynthesis is inducible by a wide range of stimuli, including metals, drugs, and inflammatory mediators. In contrast, MT-3 and MT-4 are noninducible proteins, with their expression primarily confined to the central nervous system and certain squamous epithelia, respectively. MT-1 through MT-3 have been reported to be secreted, suggesting that they may play different biological roles in the intracellular and extracellular space. Recent reports established that these isoforms play an important protective role in brain injury and metal-linked neurodegenerative diseases. In the postgenomic era, it is becoming increasingly clear that MTs fulfill multiple functions, including the involvement in zinc and copper homeostasis, protection against heavy metal toxicity, and oxidative damage. All mammalian MTs are monomeric proteins, containing two metal–thiolate clusters. In this review, after a brief summary of the historical milestones of the MT-1/MT-2 research, the recent advances in the structure, chemistry, and biological function of MT-3 and MT-4 are discussed.
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Acknowledgments
Parts of the work described in this review have been funded over the years by the Swiss National Science Foundation (M.V.). G.M. is a Marie Curie International Outgoing Fellow (European Commission, grant no. 252961).
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This article is part of a JBIC special issue on metallothioneins.
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Vašák, M., Meloni, G. Chemistry and biology of mammalian metallothioneins. J Biol Inorg Chem 16, 1067–1078 (2011). https://doi.org/10.1007/s00775-011-0799-2
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DOI: https://doi.org/10.1007/s00775-011-0799-2