Copper and zinc metallothioneins

Abstract

Metallothioneins (MTs) are a family of ubiquitous and unusual proteins which have been receiving extensive interest from chemists and biologists for the last 40 years. The first MT was discovered in 1957 by Margoshes and Vallee [1] in their search for a tissue component responsible for the natural accumulation of cadmium (Cd) in equine renal cortex. MT was so called because of its extremely high metal and sulphur contents. Aside from Cd, this protein binds other metals, especially zinc (Zn) and copper (Cu). Subsequently, researches of MTs have greatly expanded, and their presence has been demonstrated in animals, plants, fungi and cyanobacteria. MTs are characterized by the following chemical properties: (a) low molecular weight; (b) high metal content; (c) characteristic amino acid composition (high cysteine content, no aromatic amino acids); (d) characteristic distribution of cysteinyl residues; (e) spectroscopic features characteristic of metal thiolates, with arrangement of metal ions in clusters [2]. An appreciable number of MT sequences are now available. Because of the variations in their primary structures, especially location of cysteine residues and mode of synthesis, MTs are divided into three classes [2]. Class I comprise polypeptides closely related to the equine renal MT (location of cysteine similar to that of horse kidney). This includes all mammalian MTs including those from other vertebrates studied to date as well as a few from some invertebrates, such as lobster, oyster, and mussel. Class II, comprise polypeptides with location of cysteine only distantly related to that of horse kidney. The 20 known sequences belonging to this class include protists, some invertebrates (such as Drosophilia and sea urchin), cyanobacteria, yeasts and some plants. Their lengths vary from 25–101 residues and lack homology, not only among one another, but also with those of Class I. Class III are atypical MTs that are not proteins, are not translationally synthesized metal-thiolate polypeptides that contain γ-glutamyl cysteinyl units. The class is found in plants and some fungi.