Understanding the binding properties of an unusual metal-binding protein--a study of bacterial frataxin.

摘要: Deficiency of the small mitochondrial protein frataxin causes Friedreich's ataxia, a severe neurodegenerative pathology. Frataxin, which has been highly conserved throughout evolution, is thought to be involved in, among other processes, Fe–S cluster formation. Independent evidence shows that it binds iron directly, although with very distinct features and low affinity. Here, we have carried out an extensive study binding properties CyaY, bacterial ortholog frataxin, different divalent trivalent cations, using NMR X-ray crystallography. We demonstrate cation specificity contains multiple sites able chelate metals Binding does not involve cavities or pockets, but exposed glutamates aspartates, are residues unusual for chelation when assisted by histidines and/or cysteines. related how such ability bind cations on relatively large area through electrostatic mechanism could valuable asset function.