Influence of Biofilms on Migration of Uranium, Americium and Europium in the Environment
Regulation of intracellular copper homeostasis by carrier proteins is vital for all organisms, since this trace element is both essential in small quantities but deadly toxic at slightly elevated concentrations. Dysregulation can lead to a variety of severe pathologies including the genetically inherited human copper transport disorders, Menkes and Wilson disease, and is also associated with neurodegenerative diseases like Alzheimer disease. Highly conserved P-type ATPases of the PIB-subtype are the key regulators of systemic copper levels ranging from bacteria to humans. These integral membrane proteins share homology with well-known proteins like the Na+/K+-ATPase or the sarcoplasmic-reticulum Ca2+-ATPase, but differ in membrane helix topology and feature characteristic cytosolic terminal heavy metal binding domains.
Aims of the Study:
This PhD work aims at a thorough understanding of copper transporting PIB-type ATPases with a special emphasis on the intramembraneous copper binding sites. Beginning with CopA, a copper exporting PIB-type ATPase from Legionella pneumophila with recently solved structure (Gourdon, Nature, 2011, 475, 59), site directed mutagenesis and systematic truncations of the protein are intended to relate the structure to the function of the protein and to elucidate the molecular mechanisms of copper transport. Different spectroscopic approaches and micro-calorimetry as well as in vivo characterization and biochemical assays shall be used complementary. Additionally, working towards truncated or peptidic versions of the protein meeting the minimal requirements for copper binding holds great potential to shed light on the characteristics of transmembrane metal binding sites in general and to engineer such sites artificially.