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Metallothionein (MT) is a family of cysteine-rich, low molecular weight (MW ranging from 500 to 14000 Da) proteins. They are localized to the membrane of the Golgi apparatus. MTs have the capacity to bind both physiological (such as zinc, copper, selenium) and xenobiotic (such as cadmium, mercury, silver, arsenic) heavy metals through the thiol group of its cysteine residues, which represent nearly 30% of its constituent amino acid residues. MT was discovered in 1957 by Vallee and Margoshe from purification of a Cd-binding protein from horse (equine) renal cortex. MTs function is not clear, but experimental data suggest MTs may provide protection against metal toxicity, be involved in regulation of physiological metals (Zn and Cu) and provide protection against oxidative stress. There are four main isoforms expressed in humans (family 1, see chart below): MT1 (subtypes A, B, E, F, G, H, L, M, X), MT2, MT3, MT4. In the human body, large quantities are synthesised primarily in the liver and kidneys. Their production is dependent on availability of the dietary minerals, as zinc, copper and selenium, and the amino acids histidine and cysteine. == Structure and classification == MTs are present in a vast range of taxonomic groups, ranging from prokaryotes (such as the cyanobacteria ''Syneccococus spp.''...), protozoa (p. ex. the ciliate ''Tetrahymena'' genera...), plants (such as ''Pisum sativum'', ''Triticum durum'', ''Zea mays'', ''Quercus suber''...), yeast (such as ''Saccharomyces cerevisiae'', ''Candida albicans'',...), invertebrates (such as the nematode ''Caenorhabditis elegans'', the insect ''Drosophila melanogaster'', the mollusc ''Mytilus edulis'', or the echinoderm ''Strongylocentrotus purpuratus'') and vertebrates (such as the chicken, ''Gallus gallus'', or the mammalian ''Homo sapiens'' or ''Mus musculus''). The MTs from this diverse taxonomic range represent a high-heterogeneity sequence (regarding molecular weight and number and distribution of Cys residues) and do not show general homology; in spite of this, homology is found inside some taxonomic groups (such as vertebrate MTs). From their primary structure, MTs have been classified by different methods. The first one dates from 1987, when Fowler ''et al.'', established three classes of MTs: Class I, including the MTs which show homology with horse MT, Class II, including the rest of the MTs with no homology with horse MT, and Class III, which includes phytochelatins, Cys-rich enzymatically synthesised peptides. The second classification was performed by Binz and Kagi in 2001, and takes into account taxonomic parameters and the patterns of distribution of Cys residues along the MT sequence. It results in a classification of 15 families for proteinaceous MTs. Family 15 contains the plant MTs, which in 2002 have been further classified by Cobbet and Goldsbrough into 4 Types (1, 2, 3 and 4) depending on the distribution of their Cys residues and a Cys-devoid regions (called spacers) characteristic of plant MTs. A table including the principal aspects of the two latter classifications is included. More data on this classification are discoverable at the Expasy metallothionein page.〔(【引用サイトリンク】 Metallothioneins: classification and list of entries )〕 Secondary structure elements have been observed in several MTs SmtA from ''Syneccochoccus'', mammalian MT3, Echinoderma SpMTA, fish ''Notothenia Coriiceps'' MT, Crustacean MTH, but until this moment, the content of such structures is considered to be poor in MTs, and its functional influence is not considered. Tertiary structure of MTs is also highly heterogeneous. While vertebrate, echinoderm and crustacean MTs show a bidominial structure with divalent metals as Zn(II) or Cd(II) (the protein is folded so as to bind metals in two functionally independent domains, with a metallic ''cluster'' each), yeast and procariotyc MTs show a monodominial structure (one domain with a single metallic ''cluster''). Although no structural data is available for molluscan, nematoda and Drosophila MTs, it is commonly assumed that the former are bidominial and the latter monodominial. No conclusive data are available for Plant MTs, but two possible structures have been proposed: 1) a bidominial structure similar to that of vertebrate MTs; 2) a codominial structure, in which two Cys-rich domains interact to form a single metallic cluster. Quaternary structure has not been broadly considered for MTs. Dimerization and oligomerization processes have been observed and attributed to several molecular mechanisms, including intermolecular disulfide formation, bridging through metals bound by either Cys or His residues on different MTs, or inorganic phosphate-mediated interactions. Dimeric and polymeric MTs have been shown to acquire novel properties upon metal detoxification, but the physiological significance of these processes has been demonstrated only in the case of prokaryotic Synechococcus SmtA. The MT dimer produced by this organism forms structures similar to zinc fingers and has Zn-regulatory activity. Metallothioneins have diverse metal-binding preferences, which have been associated with functional specificity. As an example, the mammalian ''Mus musculus'' MT1 preferentially binds divalent metal ions (Zn(II), Cd(II),...), while yeast CUP1 is selective for monovalent metal ions (Cu(I), Ag(I),...). Strictly metal-selective MTs with metal-specific physiological functions were discovered by Dallinger et al. (1997) in pulmonate snails (Gastropoda, Mollusca).〔Dallinger R, Berger B, Hunziker P and Kägi JHR (1997). Metallothionein in snail Cd and Cu metabolism”. Nature (London) 388 (6639): 237-238〕 The Roman snail (Helix pomatia), for example, possesses a Cd-selective (CdMT) and a Cu-selective isoform (CuMT) involved in Cd detoxification and Cu regulation, respectively.〔 While both isoforms contain unvaried numbers and positions of Cys residues responsible for metal ligation, metal selectivity is apparently achieved by sequence modulation of amino acid residues not directly involved in metal binding (Palacios et al. 2011).〔〔Palacios Ò, Pagani A, Pérez-Rafael S, Egg M, Höckner M, Brandstätter A, Capdevila M, Atrian S and Dallinger R (2011). “Shaping mechanisms of metal specificity in a family of metazoan metallothioneins: evolutionary differentiation of mollusc metallothioneins”. BMC Biology 9 (4): 1-20.〕 A novel functional classification of MTs as Zn- or Cu-thioneins is currently being developed based on these functional preferences. 抄文引用元・出典: フリー百科事典『 ウィキペディア（Wikipedia）』 ■ウィキペディアで「metallothionein」の詳細全文を読む スポンサード リンク
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