Mammalian metallothioneins function

Lefebvre, D., B. Miki, and J. Laliberte, Mammalian metallothionein functions in plants. Bio-technology, 1987 5 1053-1056. 

Tamai KT, Gralla EB, Ellerby LM, Valentine JS, Thiele DJ (1993) Yeast and mammalian metallothioneins functionally substitute for yeast copper-zinc superoxide dismutase. Proc Natl Acad Sci USA 90 8013-8017... 

Tio L, Villarreal L, Atrian S, and Capdevila M (2004) Functional differentiation in the mammalian metallothionein gene family, metal binding features of mouse MT4 and comparison with its paralog MTl. Journal of... 

Metallothionein was first discovered in 1957 as a cadmium-binding cysteine-rich protein (481). Since then the metallothionein proteins (MTs) have become a superfamily characterized as low molecular weight (6-7 kDa) and cysteine rich (20 residues) polypeptides. Mammalian MTs can be divided into three subgroups, MT-I, MT-II, and MT-III (482, 483, 491). The biological functions of MTs include the sequestration and dispersal of metal ions, primarily in zinc and copper homeostasis, and regulation of the biosynthesis and activity of zinc metalloproteins. 

The recently identified brain-specific isoform of metallothionein, MT-III (neuronal growth inhibitory factor, GIF), has been linked with its potential role in neurophysiological and neuromodulatory functions (484). The human form of MT-III contains 68 amino acids with a 70% sequence (Fig. 23) similarity to other mammalian MTs and a... 

Plants contain phytoferritins, which accumulate in non-green plastids in conditions of iron loading. They are targeted to the plastids by a putative transit peptide at their N-terminal extremity, and possess the specific residues for ferroxidase activity and iron nucleation, found in mammalian H-type or L-type ferritin subunits. We already mentioned the presence of metallothioneins in photosynthetic cyanobacteria, and it comes as no surprise that metallothioneins as well as phytochelatins are found in plants where they probably function by protecting from toxic metals. 

There are two isomers of metallothionein in mammalian cells MT-1 and MT-2. There are several metallothionein genes. The transcription of each is controlled by several heavy-metal response elements or by hormone response elements [14,15]. The mechanism of control of the metallothionein genes by its promoters is a subject of intense investigation. Despite all the knowledge gained so far, the function of the metallothionein is still uncertain. However, it appears that the metallothionein may play key roles in the homeostasis of zinc within cells and in the detoxification of excess copper or toxic nonessential metals like cadmium and mercury. 

Metallothioneins (MTs) are small (6000-7000 Da), intracellular, cysteine-rich ( 33% of the amino acids are cysteines) metal binding proteins that were first discovered in 1957 in equine kidney cortex. The subsequent purification of this protein identified it as the only known native cadmium-containing protein. Further studies showed this protein to bind both essential (e.g., Cu and Zn) and nonessential (e.g., Cd and Hg) metal ions and to be truly ubiquitously distributed in nature [215-218]. Additionally, MT biosynthesis is induced at the transcriptional level by a wide range of factors, which includes heavy metal ions that were subsequently found bound to the protein. All of the above factors suggest a role for this protein in heavy metal homeostasis, transport and detoxification [215-218]. Despite 55 years of extensive studies on MTs, which has included the high resolution characterization of the 3D stmcture and metal binding properties [134,136,138,151,154,218-222], the essential physiological functional role(s) of MT remains elusive. Of particular note in these studies was the determination of the NMR solution structure of a mammalian MT in a tour deforce effort by the Wiithrich lab which resulted in the reinterpretation and correction of the mily mammalian MT crystal structure currently available [223,224]. 

---