Final Report Summary - MOTAUR (Molecular Targets of Uranium in some Aquatic Organisms)
Due to the growing number of industrial and military applications of uranium, its toxic effect is subject of concern for both human health and biology of different species. Although depleted uranium presents weak natural radioactivity, its chemical toxicity is already well documented by a number of studies of reactivity of uranyl ions in a variety of biological models leading to the formation complexes with biologically important ligands and induction of oxidative stress. However, the chemical speciation of uranium in living organisms has not been well understood on molecular level.
The MOTAUR project addressed the question of the identification of proteins and low-molecular metabolites being the targets of uranyl ions. The objective of the project was the development of novel analytical methods allowing the identification of the species resulting from interaction of uranyl ions with the proteome and metabolome. So far, most of the in-vitro studies had concerned isolated proteins, the project address the problem of U-protein interactions in a system in their globality, including protein-uranyl ion-protein complex interactions. The characterization of these interactions on a large scale was the focus of the project.
The results indicate that uranyl ions impacts a serum protein network as a binding ligand rather than chooses single molecular targets. For this reason the proteomics data were characterized in terms of molecular and biological functions of involved proteins, e.g. coagulation cascades, mineralization and metal ions binding.
Proteins identified on the basis of their reactivity towards uranyl ions constitute a rich interaction network (observed 144, expected 91). Further analysis indicated that 32 of those proteins were responsible for protein binding and 34 - for interactions with the ions (with both cations and anions); this finding is in good correlation with the literature information that uranyl ion can be bound in both cationic and anionic form. Proteins which are involved in homeostasis of other ions (mostly calcium) have also been detected. Interestingly, some of them contained GLA (gamma-carboxyglutamic acid) rich domains which showed high affinity toward calcium ions and so far have not been considered as targets of uranyl ions in serum. In the uranyl ions dependent network eight proteins are known for binding heparin which, as a sulfate rich ligand, can easily interact with the uranyl ion (similarly to calcium ions). The relation of other elements present in serum, including Ca, P and Mg, with uranium dependent proteins were characterized as well. The difference in isolated protein pattern in case of bovine and foetal sera system indicate different molecular mechanisms of binding of uranyl ions showing the validity of our method a variety of sera samples. The details of the most important findings of the MOTAUR project have been described in the publication (Szyrwiel L. et al. Metallomics, 2015, 7, 1604-1611).
The MOTAUR project addressed the question of the identification of proteins and low-molecular metabolites being the targets of uranyl ions. The objective of the project was the development of novel analytical methods allowing the identification of the species resulting from interaction of uranyl ions with the proteome and metabolome. So far, most of the in-vitro studies had concerned isolated proteins, the project address the problem of U-protein interactions in a system in their globality, including protein-uranyl ion-protein complex interactions. The characterization of these interactions on a large scale was the focus of the project.
The results indicate that uranyl ions impacts a serum protein network as a binding ligand rather than chooses single molecular targets. For this reason the proteomics data were characterized in terms of molecular and biological functions of involved proteins, e.g. coagulation cascades, mineralization and metal ions binding.
Proteins identified on the basis of their reactivity towards uranyl ions constitute a rich interaction network (observed 144, expected 91). Further analysis indicated that 32 of those proteins were responsible for protein binding and 34 - for interactions with the ions (with both cations and anions); this finding is in good correlation with the literature information that uranyl ion can be bound in both cationic and anionic form. Proteins which are involved in homeostasis of other ions (mostly calcium) have also been detected. Interestingly, some of them contained GLA (gamma-carboxyglutamic acid) rich domains which showed high affinity toward calcium ions and so far have not been considered as targets of uranyl ions in serum. In the uranyl ions dependent network eight proteins are known for binding heparin which, as a sulfate rich ligand, can easily interact with the uranyl ion (similarly to calcium ions). The relation of other elements present in serum, including Ca, P and Mg, with uranium dependent proteins were characterized as well. The difference in isolated protein pattern in case of bovine and foetal sera system indicate different molecular mechanisms of binding of uranyl ions showing the validity of our method a variety of sera samples. The details of the most important findings of the MOTAUR project have been described in the publication (Szyrwiel L. et al. Metallomics, 2015, 7, 1604-1611).