An analysis of surface proteomics results reveals novel candidates for intracellular/surface moonlighting proteins in bacteria

Mol Biosyst. 2016 Apr 26;12(5):1420-31. doi: 10.1039/c5mb00550g.


Proteins expressed on the bacterial cell surface play important roles in infection and virulence and can be targets for vaccine development or used as biomarkers. Surprisingly, an increasing number of surface proteins are being found to be identical to intracellular enzymes and chaperones, and a few dozen intracellular/surface moonlighting proteins have been found that have different functions inside the cell and on the cell surface. The results of twenty-two published bacterial surface proteomics studies were analyzed using bioinformatics tools to consider how many additional intracellular proteins are also found on the cell surface. More than 1000 out of the 3619 proteins observed on the cell surface lack the transmembrane alpha-helices or transmembrane beta-barrels found in integral membrane proteins and also lack the signal peptides found in proteins secreted through the Sec pathway. Many of the proteins found on the cell surface are intracellular chaperones or enzymes involved in central metabolic pathways, including some that have previously been shown to have a moonlighting function on the cell surface in at least one species, such as Hsp60/GroEL, DnaK, glyceraldehyde 3-phosphate dehydrogenase, enolase, and fructose 1,6-bisphosphate aldolase. The results of the proteomics studies suggest they could also be moonlighting on the surface of many other species. Hundreds of other intracellular proteins are also found on the cell surface, although a second function on the surface has not yet been demonstrated, for example, glutamine synthetase, gamma-glutamyl phosphate reductase, and cysteine desulfurase. The presence of intracellular proteins on the cell surface is more common than previously expected and suggests that many additional proteins might be candidates for being intracellular/surface moonlighting proteins.

Publication types

  • Meta-Analysis
  • Review

MeSH terms

  • Bacteria / metabolism
  • Bacterial Proteins / chemistry
  • Bacterial Proteins / metabolism*
  • Cell Membrane / metabolism
  • Cytoplasm / metabolism
  • Databases, Protein
  • Membrane Proteins / chemistry
  • Membrane Proteins / metabolism*
  • Protein Interaction Domains and Motifs
  • Proteome*
  • Proteomics* / methods


  • Bacterial Proteins
  • Membrane Proteins
  • Proteome