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Chemistry and biology of mammalian metallothioneins

Vašák, Milan and Meloni, Gabriele (2011) Chemistry and biology of mammalian metallothioneins. Journal of Biological Inorganic Chemistry, 16 (7). pp. 1067-1078. ISSN 0949-8257.

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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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Additional Information:© 2011 SBIC. Received: 30 March 2011. Accepted: 12 May 2011. Published online: 7 June 2011. 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).
Funding AgencyGrant Number
Swiss National Science Foundation (SNSF)UNSPECIFIED
European Commission252961
Subject Keywords:Zinc; Copper; Mammalian metallothioneins; Metal–thiolate clusters; Neurodegenerative diseases
Issue or Number:7
Record Number:CaltechAUTHORS:20111012-082018476
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Official Citation:Chemistry and biology of mammalian metallothioneins Milan Vašák and Gabriele Meloni
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:27176
Deposited By: Ruth Sustaita
Deposited On:12 Oct 2011 15:37
Last Modified:03 Oct 2019 03:21

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