Promiscuous Nickel Import in Human Pathogens: Structure, Thermodynamics, and Evolution of Extracytoplasmic Nickel-Binding Proteins

• Three nickel-binding proteins (Ni-BP) from human pathogens have been characterized
• The identification of 3 Ni-binding motifs supports a variegated ligand selectivity
• Hypothesis of a general requirement of nickelophores for nickel uptake is challenged
• Phylogenetic analyses possibly explain the promiscuous behavior of Ni-BPs

SummaryIn human pathogenic bacteria, nickel is required for the activation of two enzymes, urease and [NiFe]-hydrogenase, necessary for host infection. Acquisition of Ni(II) is mediated by either permeases or ABC-importers, the latter including a subclass that involves an extracytoplasmic nickel-binding protein, Ni-BP. This study reports on the structure of three Ni-BPs from a diversity of human pathogens and on the existence of three new nickel-binding motifs. These are different from that previously described for Escherichia coli Ni-BP NikA, known to bind nickel via a nickelophore, and indicate a variegated ligand selectivity for Ni-BPs. The structures are consistent with ligand affinities measured in solution by calorimetry and challenge the hypothesis of a general requirement of nickelophores for nickel uptake by canonical ABC importers. Phylogenetic analyses showed that Ni-BPs have different evolutionary origins and emerged independently from peptide-binding proteins, possibly explaining the promiscuous behavior of this class of Ni(II) carriers.

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