Metallothionein

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Structure of a-domain of Human Metallothionein-3 (MT-3) with Cd-Cd bond

Mechanism of Nrf2 and MT in preventing IH-induced cardiac injury.

Metallothionein is a family of proteins characterized by their high content of cysteine residues and their ability to bind metal ions. These proteins play a crucial role in the metabolism of essential metals such as zinc and copper, as well as in the detoxification of heavy metals like cadmium, mercury, and lead. Metallothioneins are found in virtually all organisms, from bacteria to humans, highlighting their importance in biological systems.

Structure and Function

Metallothioneins are low-molecular-weight proteins, typically consisting of 61 to 68 amino acids, including 20 cysteine residues but no aromatic amino acids or histidine. The high content of cysteine allows these proteins to form thiolate clusters, which can bind metal ions through mercaptide linkages. This unique structure enables metallothioneins to sequester metal ions, thereby regulating their concentration and availability in the cell.

The primary function of metallothioneins is the homeostasis of essential metals. They play a significant role in the storage and release of zinc and copper, which are vital for numerous biological processes, including enzyme activity and gene expression. Metallothioneins can also protect cells from the toxic effects of heavy metals by binding and neutralizing them. This detoxification mechanism is critical in environments contaminated with heavy metals, where it helps to prevent metal poisoning.

Classification

Metallothioneins are classified into several isoforms, based on their sequence homology and metal-binding patterns. In mammals, four major isoforms (MT-1 to MT-4) have been identified, each with distinct expression patterns and functions. MT-1 and MT-2 are the most widely expressed and are involved in metal ion metabolism and detoxification. MT-3, initially identified in the brain, has a specific role in the nervous system and has been implicated in neurodegenerative diseases such as Alzheimer's disease. MT-4 is primarily expressed in stratified squamous epithelia, where it is thought to play a role in skin and mucosal protection.

Biological Significance

The ability of metallothioneins to bind metals is not only crucial for detoxification and homeostasis but also plays a role in protecting cells against oxidative stress. Metals like copper and iron can catalyze the formation of free radicals, leading to oxidative damage. By sequestering these metals, metallothioneins prevent their participation in harmful redox reactions.

Furthermore, metallothioneins have been implicated in various human diseases and conditions. Alterations in metallothionein expression have been observed in cancer, where they may contribute to tumor growth and resistance to chemotherapy. In contrast, their role in metal detoxification has been explored as a potential therapeutic strategy for heavy metal poisoning.

Research and Applications

Research on metallothioneins continues to uncover their multifaceted roles in biology and medicine. Their potential applications in biotechnology and medicine include biomarkers for metal exposure and disease, therapeutic agents for metal detoxification, and targets for the treatment of metal-related diseases.