Metallothionein

Metallothionein superfamily (plant)
Beta-E-domain of wheat Ec-1 metallothionein bound to zinc ions. Cysteines in yellow, zinc in purple. (PDB: 2KAK​)[1]
Identifiers
SymbolMetallothionein_sfam
PfamPF00131
InterProIPR003019
Available protein structures:
Pfam  structures / ECOD  
PDBRCSB PDB; PDBe; PDBj
PDBsumstructure summary
PDBPDB: 1dfs​ PDB: 1dft​ PDB: 1dmc​ PDB: 1dmd​ PDB: 1dme​ PDB: 1dmf​ PDB: 1j5l​ PDB: 1j5m​ PDB: 1ji9​ PDB: 1m0g​
Yeast MT
Saccharomyces cerevisiae MT metallothionein bound to copper ions. Cysteines in yellow, copper in brown. (PDB: 1AQS​)
Identifiers
SymbolYeast metallothionein
PfamPF11403
Pfam clanCL0461
InterProIPR022710
Available protein structures:
Pfam  structures / ECOD  
PDBRCSB PDB; PDBe; PDBj
PDBsumstructure summary
Cyanobacterial SmtA
Cyanobacterial SmtA metallothionein bound to zinc ions. Cysteines in yellow, zinc in purple. (PDB: 1JJD​)
Identifiers
SymbolBacterial metallothionein
PfamPF02069
Pfam clanCL0461
InterProIPR000518
Available protein structures:
Pfam  structures / ECOD  
PDBRCSB PDB; PDBe; PDBj
PDBsumstructure summary

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, lead) heavy metals through the thiol group of its cysteine residues, which represent nearly 30% of its constituent amino acid residues.[2]

MT was discovered in 1957 by Vallee and Margoshe from purification of a Cd-binding protein from horse (equine) renal cortex.[3] MT plays a role in the protection against metal toxicity and oxidative stress, and is involved in zinc and copper regulation.[4] 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, and 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 such as zinc, copper, and selenium, as well as the amino acids histidine and cysteine.

Metallothioneins are rich in thiols, causing them to bind a number of trace metals. Metallothionein is one of the few eukaryotic proteins playing a substantial role in metal detoxification. Zinc and Cadmium are tetrahedrally coordinated to cysteine residues, and each metallothionein protein molecule may bind up to 7 atoms of Zn or Cd.[5] The biosynthesis of metallothionein appears to increase several-fold during periods of oxidative stress to shield the cells against cytotoxicity and DNA damage. Metallothionein biosynthesis can also be induced by certain hormones, pharmaceuticals, alcohols, and other compounds.[6] Metallothionein expression is upregulated during fetal development, particularly in liver tissue.[7]

  1. ^ PDB: 2KAK​; Peroza EA, Schmucki R, Güntert P, Freisinger E, Zerbe O (March 2009). "The beta(E)-domain of wheat E(c)-1 metallothionein: a metal-binding domain with a distinctive structure". Journal of Molecular Biology. 387 (1): 207–18. doi:10.1016/j.jmb.2009.01.035. PMID 19361445.
  2. ^ Sigel H, Sigel A, eds. (2009). Metallothioneins and Related Chelators (Metal Ions in Life Sciences). Vol. 5. Cambridge, England: Royal Society of Chemistry. ISBN 978-1-84755-899-2.
  3. ^ Margoshes M, Vallee BL (1957). "A cadmium protein from equine kidney cortex". Journal of the American Chemical Society. 79 (17): 4813–4814. doi:10.1021/ja01574a064.
  4. ^ Felizola SJ, Nakamura Y, Arata Y, Ise K, Satoh F, Rainey WE, Midorikawa S, Suzuki S, Sasano H (September 2014). "Metallothionein-3 (MT-3) in the human adrenal cortex and its disorders". Endocrine Pathology. 25 (3): 229–35. doi:10.1007/s12022-013-9280-9. PMID 24242700. S2CID 39871076.
  5. ^ Suhy DA, Simon KD, Linzer DI, O'Halloran TV (April 1999). "Metallothionein is part of a zinc-scavenging mechanism for cell survival under conditions of extreme zinc deprivation". The Journal of Biological Chemistry. 274 (14): 9183–92. doi:10.1074/jbc.274.14.9183. PMID 10092590.
  6. ^ Wang WC, Mao H, Ma DD, Yang WX (August 2014). "Characteristics, functions, and applications of metallothionein in aquatic vertebrates". Frontiers in Marine Science. 1: 34. doi:10.3389/fmars.2014.00034.
  7. ^ Cherian MG (September 1994). "The significance of the nuclear and cytoplasmic localization of metallothionein in human liver and tumor cells". Environmental Health Perspectives. 102 (Suppl 3): 131–5. doi:10.2307/3431776. JSTOR 3431776. PMC 1567399. PMID 7843087.