Intrinsic disorder regulates nickel trafficking in the urease system

Nickel is a toxic element for cellular life, but is also an important micronutrient in several biological processes. Urease is an essential nickel-enzyme for many pathogens and soil microorganisms. The incorporation of nickel into the urease active site requires the interplay of four accessory proteins, named UreD, UreE, UreF and UreG. UreG is an intrinsically unstructured GTPase, essential for providing energy to the process of nickel site assembly. The hydrodynamic, functional and structural properties of UreG from different organisms were investigated using light scattering, circular dichroism, NMR, fluorescence spectroscopy and computational approaches. Our results strongly suggest that protein disorder plays an important function for the regulation of intracellular nickel trafficking leading to urease activation. This consideration is further supported by the discovery of a new possible role for UreF as a GTP-ase activating protein, possibly promoting the folding and the activation of UreG. Recently, new data demonstrated that UreE also interacts with UreG in a tetrameric hetero-complex.