Lead


Lay summary
This scientific project is divided into two, largely independent subjects. focuses on the metal ion binding abilities of plant metallothioneins (MTs) and related artificial proteins, including the investigation of their structures and general properties. Metal ions are essential for life but depending on the concentration and sort of metal ion they can also exhibit a considerable amount of toxicity. The tight regulation of reactive transition metal ions resulting in free metal ion concentrations of below one ion per cell is essential for the survival of any living organism. One protein superfamily that is taking part in these uptake, transport and accumulation mechanisms inside the cell are the MTs. Generally, MTs are a family of small proteins with an outstandingly high content of the amino acid cysteine and metal ions with the electronic configuration d10. In a way, MTs might be regarded as inorganic metal-thiolate clusters embedded in a biological matrix and are thus one of the classical examples out of the research field of Bioinorganic Chemistry. MTs from plants have been scarcely studied so far. They have a proposed role in metal ion homeostasis, detoxification, and plant development, although final evidence in this regard is still pending. Differing considerably in their primary amino acid sequences from the well-studied mammalian isoforms, different properties and new exciting three-dimensional structures can be foreseen. This new knowledge might even allow us to optimize the metal ion binding properties or even metal ion specificity of these proteins. Plants, over-expressing such specialized proteins, might be able to grow in polluted areas or might be used to specifically remove heavy metal ions from the environment (phytoremidation), e.g. from mining areas and land used by heavy metal releasing manufacturing industry. of the research project concerns research on nucleic acids. Modification of the nucleic acid building blocks, especially the nucleobases, is up to now either not very site specific, e.g. complete modification of a certain nucleobase type throughout the whole sequence occurs, or depends on solid-phase synthesis. The latter method is costly for longer nucleic acids and often restricted to the incorporation of modified nucleotides at or near the end of the sequence, again due to economic reasons. The approach described here will allow the site-specific modification of nucleotides in DNA or RNA of unrestricted length. Such specifically modified larger oligonucleotides will then open up new ways to investigate the specific effect of natural modifications and lesions on structure and function of DNA and RNA.