| MT-1 is an isoform of the ubiquitously occurring metalloproteins characterized by a high metal and cysteine sulphur content. It is composed of a single polypeptide chain of 61 amino acids, 20 of which are cysteine residues and none of which are aromatic amino acids or histidine. The MT-1 fraction contains additional MT isoforms, which differ only in amino acid residues other than Cys. They are similar in sequence and therefore also in charge. The 3D structure of the metal complex contains two separate domains, alpha and beta. The alpha-domain encloses four bivalent metal ions in the form of a Me4Cys11 cluster. The beta-domain contains an analogous Me3Cys9 cluster. Monovalent metal ions like Cu(I) can form a cluster as well, via thiolate bonds. Much of our understanding of the biological actions of MTs has arisen from the comparative analysis of the chemical and structural features. MT-1 is expressed in almost all tissues. It is a cytosolic protein, which is up-regulated in response to many factors, including metals, hormones, inflammation related stimuli (cytokines), and stressful reagents. It is suggested that it has multiple biological roles such as, regulatory role of Zn-metabolism (zinc-finger transcription factors), regulation of metal-exchange detoxification (marker for heavy metal intoxication), protection against reactive oxygen species (ROS), adaptation to stress, anti-apoptotic effects (activation of NF-κB/interaction with p50 subunit), and in protection against anticancer treatments. [2, 3] |
