Maintaining proper metal ion homeostasis is key to the survival of all organisms. In particular, the viability of many bacterial pathogens is linked to metal acquisition. The proteins that are involved in maintaining metal homeostasis control import and export (metallotransporters), target the delivery of metals to specific enzymes (metallochaperones), are involved in metallocenter assembly (accessory proteins), and regulate the expression of the other proteins in response to metal ion availability (metalloregulators). When metal-trafficking malfunctions several disease states result.
For example, Wilson’s and Menkes diseases result from defects in copper trafficking, and hemochromatosis and other hereditary iron overload diseases are the result of defects in iron trafficking. Neurological diseases, including Alzheimer’s and Parkinson’s, have been associated with mis-trafficking of metals, which can result in the misfolding and aggregation of proteins.
The Metal Homeostasis subtheme takes a structure-function approach to understanding metal-protein interactions. Structural tools used include x-ray absorption spectroscopy (XAS, Maroney) and mass spectrometry (Vachet) to probe metal site structure, x-ray diffraction (XRD, Garman) for protein structure determination, NMR for protein structure and dynamics (Gierasch), and non-denaturing mass spectrometry (Kaltashov and Vachet) to probe relevant protein-protein and protein-DNA interactions.