A Salmonella typhimurium effector protein SifA is modified by host cell prenylation and S-acylation machinery

J Biol Chem. 2005 Apr 15;280(15):14620-7. doi: 10.1074/jbc.M500076200. Epub 2005 Feb 14.


SifA is a Salmonella effector protein that is required for maintenance of the vacuolar membrane that surrounds replicating bacteria. It associates with the Salmonella-containing vacuole but how it interacts with the membrane is unknown. Here we show by immunofluorescence, S100 fractionation and Triton X-114 partitioning that the membrane association and targeting properties of SifA are influenced by a motif encoded within the C-terminal six amino acids. This sequence shares homology with both CAAX and Rab geranylgeranyl transferase prenylation motifs. We characterized the post-translational processing of SifA and showed that the cysteine residue within the CAAX motif is modified by isoprenoid addition through the action of protein geranylgeranyl transferase I. SifA was additionally modified by S-acylation of an adjacent cysteine residue. Similar modifications to host cell proteins regulate numerous functions including protein targeting, membrane association, protein-protein interaction, and signal transduction. This is the only known example of a bacterial effector protein that is modified both by mammalian cell S-acylation and prenylation machinery.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acylation
  • Alkyl and Aryl Transferases / metabolism
  • Amino Acid Motifs
  • Amino Acid Sequence
  • Animals
  • Bacterial Proteins / chemistry
  • Bacterial Proteins / physiology*
  • Carbonates / pharmacology
  • Cell Line
  • Cell Membrane / metabolism
  • Cysteine / chemistry
  • Cytosol / metabolism
  • Detergents / pharmacology
  • Electrophoresis, Polyacrylamide Gel
  • Glycoproteins / chemistry
  • Glycoproteins / physiology*
  • Green Fluorescent Proteins / metabolism
  • Humans
  • Immunoblotting
  • Macrophages / metabolism
  • Mice
  • Microscopy, Fluorescence
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Oligonucleotides / chemistry
  • Plasmids / metabolism
  • Polyethylene Glycols / pharmacology
  • Protein Biosynthesis
  • Salmonella typhimurium / metabolism*
  • Sequence Homology, Amino Acid
  • Subcellular Fractions
  • Time Factors
  • Transfection


  • Bacterial Proteins
  • Carbonates
  • Detergents
  • Glycoproteins
  • Oligonucleotides
  • SifA protein, Salmonella
  • Green Fluorescent Proteins
  • Polyethylene Glycols
  • sodium carbonate
  • Nonidet P-40
  • Alkyl and Aryl Transferases
  • geranylgeranyltransferase type-I
  • Cysteine