Study of the interaction between actinides and peptide ligands

International audience ; Actinides are radioactive metals of high importance in civil and military nuclear activities. Trace amounts of these elements may be found in the environment due to historical nuclear tests and accidental releases. Most actinides being alpha emitters, it is essential to investigate their behavior within the human body. While the targeted organs are well-known, the transport mechanism and molecular interactions remain unidentified. Proteins have been identified as actinide targets in the event of human contamination. Although the literature on the interactions between actinides and proteins is scarce, metalloproteomic studies have shown that several calcium-binding proteins have a strong affinity for actinides. As a model for all calciumbinding protein, the calcium-modulated protein (calmodulin) was chosen for its EF-hand motif site, which is widely present in calcium-biding proteins, and its high importance in cellular regulatory function. L. Daronnat investigated the interaction of plutonium (IV) with several variants of the calmodulin and observed various behaviors of the plutonium depending on the variant of calmodulin used2 : the formation of a Pu(IV)-calmodulin complex, the formation of a Pu(III)-calmodulin complex and the formation of hexanuclear clusters of plutonium. CaME (Engineered Calmodulin) is a variant of calmodulin developed especially to bind plutonium(IV). This variant has an extra carboxylate ligand in its complexation loop (shown in figure 1), increasing its affinity for actinides IV. This particular variant was the only which did not promote the formation of plutonium clusters. Instead, it only generated 1:1 complexes. Additionally, an unexpected change of the oxidation state of plutonium (from IV to III) was noticed in presence of CaME. To get a better understanding of this behavior, a deepened characterization of the species formed between CaME and actinides have been undertaken. This work aims to characterize the complexes formed between CaME and actinides (Th, U, ...