Copper metallothioneins

Abstract

Metallothioneins (MTs) are a class of low molecular weight and cysteine-rich metal binding proteins present in all the branches of the tree of life. MTs efficiently bind with high affinity several essential and toxic divalent and monovalent transition metals by forming characteristic polynuclear metalthiolate clusters within their structure. MTs fulfil multiple biological functions related to their metal binding properties, with essential roles in both Zn(II) and Cu(I) homeostasis as well as metal detoxification. Depending on the organism considered, the primary sequence, and the specific physiological and The presence of nonsulfur coordination residues (e.g., histidine) in some members of the superfamily, such as bacterial and plant MTs, has broken the dogma of the exclusive metal coordination by cysteine thiolate residues in MTs. According to Binz and K€ agi (2), MTs are classified into 15 families based on taxonomic parameters and the patterns of distribution of Cys residues in their sequence. The recognized fundamental functions of MTs arise from their capabilities to bind transition metals with high affinity, and their primary biological roles include homeostasis of essential trace metals zinc and copper, and sequestration and protection from environmental toxic metals such as cadmium, mercury, and lead (1). In addition, in light of the reactivity of the metal-coordinating thiolate ligands, MTs play fundamental roles in protection against oxidative stress including reactive oxygen and nitrogen species and other free radicals (1,3-5). However, additional specific MT functions arise from specific biological needs and complexity of the organisms in which they are expressed. Since 60 years from their discovery, it emerged that metallothoineins indeed possess complex pleiotropic functions. This is exemplified by the better-studied mammalian MTs for which additional specialized roles in adaptation to stress, protection against brain injury, regulation of neuronal outgrowth, antiapoptotic effects, and reactivity and inactivation of metal-based chemotherapeutics leading to resistance have been demonstrated (4).As a result of the high number of thiolate coordinating residues in MTs and the lack of defined three-dimensional (3D) structures in the metal depleted apo forms, MTs can bind a number of different monovalent and divalent metals both in vitro and in vivo. The affinity of the metal ions for the binding

Mammalian Metallothionein-3: New Functional and Structural Insights

“…A similar conclusion has been drawn from computational studies in which, in the absence of metallochaperons, the local metal concentrations were found critical for the metal specificity of proteins [37]. Although the enhanced copper-thionein character of MT-3 over MT-1/-2 may still, in part, reflect subtle differences between the two sequences and consequently their structural properties [38], it would appear that the reported metal binding preference of various MTs in E. coli cultures may not exactly reflect the buffered metal concentrations present in different mammalian cell types where the MT biosynthesis occurs.…”

Enhanced Silver Nanoparticle Synthesis by Escherichia Coli Transformed with Candida Albicans Metallothionein Gene

“…Cells were spun down and resuspended in 100 mL of LB with 100 µg/mL carbenicillin. Optical density at 600 nm (OD 600nm ) was monitored each hour after resuspension until OD 600nm reached between 0.6 and 0.8, then OD 600nm was measured at 24 h, 48 h and 72 h. It has been shown that MT expression was induced and upregulated when microorganisms are under heavy metal stress [5,6,17,18]. To further investigate whether the expression of C. albicans MT in E. coli impact the bacterial tolerance to heavy metal, we cultivated the bacteria in the presence of 0.2 mM CuSO 4 .…”

“…In particular, there is an increasing interest in the exploitation of the cysteine-rich metal-binding proteins, metallothioneins (MTs), in the development of biofactories for metal NP production. MTs are found in all eukaryotes, as well as some prokaryotes, and play an important role in intracellular metal distribution, accumulation, as well as protection of cells against heavy metal toxicity and oxidative stress [5,6]. The Cys-Xaa-Cys clusters of MTs can act as a reducing functional group for the reduction of metal ions, chelation, and accumulation of metal particles in the cells [5][6][7].…”

“…MTs are found in all eukaryotes, as well as some prokaryotes, and play an important role in intracellular metal distribution, accumulation, as well as protection of cells against heavy metal toxicity and oxidative stress [5,6]. The Cys-Xaa-Cys clusters of MTs can act as a reducing functional group for the reduction of metal ions, chelation, and accumulation of metal particles in the cells [5][6][7]. Studies showed that MTs are involved in the detoxification of several metals, including zinc, mercury, copper and cadmium in microorganisms [5,6,8].…”

“…The Cys-Xaa-Cys clusters of MTs can act as a reducing functional group for the reduction of metal ions, chelation, and accumulation of metal particles in the cells [5][6][7]. Studies showed that MTs are involved in the detoxification of several metals, including zinc, mercury, copper and cadmium in microorganisms [5,6,8]. Due to their important role in metal reduction and high metal binding affinity,…”