Metallomics reveals a persisting impact of cadmium on the evolution of metal-selective snail metallothioneins.

The tiny contribution of cadmium (Cd) to the composition of the earth's crust contrasts with its high biological significance, owing mainly to the competition of Cd with the essential zinc (Zn) for suitable metal binding sites in proteins. In this context it was speculated that in several animal lineages, the protein family of metallothioneins (MTs) has evolved to specifically detoxify Cd. Although the multi-functionality and heterometallic composition of MTs in most animal species does not support such an assumption, there are some exceptions to this role, particularly in animal lineages at the roots of animal evolution.

The Solution Structure and Dynamics of Cd-Metallothionein from Reveal Optimization for Binding Cd over Zn.

Metallothioneins (MTs) are cysteine-rich polypeptides that are naturally found coordinated to monovalent and/or divalent transition metal ions. Three metallothionein isoforms from the Roman snail are known. They differ in their physiological metal load and in their specificity for transition metal ions such as Cd (HpCdMT isoform) and Cu (HpCuMT isoform) or in the absence of a defined metal specificity (HpCd/CuMT isoform).

Mouse metallothionein-1 and metallothionein-2 are not biologically interchangeable in an animal model of multiple sclerosis, EAE.

Mouse metallothionein-1 and 2 (MT1 and MT2) are often considered physiologically equivalent, because they are normally regulated coordinately by a wide range of stimuli, and it is assumed that in vivo they will be normally fully loaded with zinc(ii) (Zn7-MT1/2), although other metal ions, such as copper(i), may be eventually found as well. However, mouse MT2, in contrast to MT1, exhibits a preference for Zn(ii) coordination in comparison to that for Cu(i), which might underlie putatively different biological functions for these two mammalian isoforms. We have characterized the effects of exogenously administered mouse MT1 and MT2, and of transgenic Mt1 overexpression, in an animal model of multiple sclerosis (MS), experimental autoimmune encephalomyelitis (EAE), by active immunization with MOG35-55 peptide.

Copper redox chemistry of plant frataxins.

The presence of a conserved cysteine residue in the C-terminal amino acid sequences of plant frataxins differentiates these frataxins from those of other kingdoms and may be key in frataxin assembly and function. We report a full study on the ability of Arabidopsis (AtFH) and Zea mays (ZmFH-1 and ZmFH-2) frataxins to assemble into disulfide-bridged dimers by copper-driven oxidation and to revert to monomers by chemical reduction. We monitored the redox assembly-disassembly process by electrospray ionization mass spectrometry, electrophoresis, UV-Vis spectroscopy, and fluorescence measurements.

Biomphalaria glabrata Metallothionein: Lacking Metal Specificity of the Protein and Missing Gene Upregulation Suggest Metal Sequestration by Exchange Instead of through Selective Binding.

The wild-type metallothionein (MT) of the freshwater snail and a natural allelic mutant of it in which a lysine residue was replaced by an asparagine residue, were recombinantly expressed and analyzed for their metal-binding features with respect to Cd, Zn and Cu⁺, applying spectroscopic and mass-spectrometric methods. In addition, the upregulation of the gene was assessed by quantitative real-time detection PCR. The two recombinant proteins revealed to be very similar in most of their metal binding features.