Promiscuous nickel import in human pathogens: structure, thermodynamics, and evolution of extracytoplasmic nickel-binding proteins

Structure. 2014 Oct 7;22(10):1421-32. doi: 10.1016/j.str.2014.07.012. Epub 2014 Sep 4.


In 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs
  • Amino Acid Sequence
  • Bacterial Proteins / chemistry*
  • Bacterial Proteins / metabolism
  • Binding Sites
  • Biological Transport
  • Brucella suis / chemistry
  • Brucella suis / pathogenicity
  • Campylobacter jejuni / chemistry
  • Campylobacter jejuni / pathogenicity
  • Carrier Proteins / chemistry*
  • Carrier Proteins / metabolism*
  • Crystallography, X-Ray
  • Evolution, Molecular*
  • Models, Molecular
  • Molecular Sequence Data
  • Nickel / metabolism*
  • Phylogeny
  • Protein Conformation
  • Thermodynamics
  • Yersinia pestis / chemistry
  • Yersinia pestis / pathogenicity


  • Bacterial Proteins
  • Carrier Proteins
  • Nickel