FhuD1, a ferric hydroxamate-binding lipoprotein in Staphylococcus aureus: a case of gene duplication and lateral transfer

J Biol Chem. 2004 Dec 17;279(51):53152-9. doi: 10.1074/jbc.M409793200. Epub 2004 Oct 8.

Abstract

Staphylococcus aureus can utilize ferric hydroxamates as a source of iron under iron-restricted growth conditions. Proteins involved in this transport process are: FhuCBG, which encodes a traffic ATPase; FhuD2, a post-translationally modified lipoprotein that acts as a high affinity receptor at the cytoplasmic membrane for the efficient capture of ferric hydroxamates; and FhuD1, a protein with similarity to FhuD2. Gene duplication likely gave rise to fhuD1 and fhuD2. While the genomic locations of fhuCBG and fhuD2 in S. aureus strains are conserved, both the presence and the location of fhuD1 are variable. The apparent redundancy of FhuD1 led us to examine the role of this protein. We demonstrate that FhuD1 is expressed only under conditions of iron limitation through the regulatory activity of Fur. FhuD1 fractions with the cell membrane and binds hydroxamate siderophores but with lower affinity than FhuD2. Using small angle x-ray scattering, the solution structure of FhuD1 resembles that of FhuD2, and only a small conformational change is associated with ferrichrome binding. FhuD1, therefore, appears to be a receptor for ferric hydroxamates, like FhuD2. Our data to date suggest, however, that FhuD1 is redundant to FhuD2 and plays a minor role in hydroxamate transport. However, given the very real possibility that we have not yet identified the proper conditions where FhuD1 does provide an advantage over FhuD2, we anticipate that FhuD1 serves an enhanced role in the transport of untested hydroxamate siderophores and that it may play a prominent role during the growth of S. aureus in its natural environments.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biological Assay
  • Cell Membrane / metabolism
  • Cell Proliferation
  • Cytoplasm / metabolism
  • Detergents / pharmacology
  • Endopeptidase K / pharmacology
  • Evolution, Molecular
  • Gene Duplication*
  • Gene Transfer Techniques
  • Hydroxamic Acids / chemistry*
  • Intracellular Membranes / metabolism
  • Iron / chemistry*
  • Iron / metabolism
  • Kinetics
  • Lipoproteins / chemistry*
  • Lipoproteins / genetics*
  • Membrane Transport Proteins / chemistry
  • Membrane Transport Proteins / genetics*
  • Models, Genetic
  • Phylogeny
  • Protein Binding
  • Protein Conformation
  • Protein Processing, Post-Translational
  • Scattering, Radiation
  • Siderophores / metabolism
  • Staphylococcus aureus / genetics*
  • Staphylococcus aureus / metabolism
  • X-Rays

Substances

  • Detergents
  • Hydroxamic Acids
  • Lipoproteins
  • Membrane Transport Proteins
  • Siderophores
  • Iron
  • Endopeptidase K