Human intestinal TFF3 forms disulfide-linked heteromers with the mucus-associated FCGBP protein and is released by hydrogen sulfide

J Proteome Res. 2010 Jun 4;9(6):3108-17. doi: 10.1021/pr100020c.


TFF3 is a secretory peptide belonging to the trefoil factor family with a predicted size of 59 amino acid residues containing seven cysteine residues. It is predominantly expressed in intestinal goblet cells where it plays a key role in mucosal regeneration and repair processes. In the course of these studies, human colonic TFF3 was shown to exist mainly as a high molecular weight heteromer. Purification of this heteromer and characterization by LC-ESI-MS/MS analysis identified the IgG Fc binding protein (FCGBP) as the disulfide-linked partner protein of TFF3. FCGBP is a constituent of intestinal mucus secreted by goblet cells. Furthermore, low amounts of TFF3/monomer and only little TFF3/dimer were detected in human colonic extracts. Here, we show that these TFF3 forms can be released from the purified TFF3-FCGBP heteromer complex in vitro by reduction with hydrogen sulfide (H(2)S). Such a mechanism would be in line with the high H(2)S concentrations reported to occur in the lumen of the colon. Of special note, this points to intestinal mucus as a reservoir for a biologically active peptide. Also proteolytic processing of FCGBP was observed which is in line with multiple autocatalytic cleavages as proposed earlier by Johansson et al. (J. Proteome Res. 2009 , 8 , 3549 - 3557).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • Cell Adhesion Molecules / chemistry*
  • Cell Adhesion Molecules / metabolism
  • Chromatography, Gel
  • Colon / chemistry
  • Colon / metabolism
  • Humans
  • Hydrogen Sulfide / metabolism*
  • Mucus / metabolism
  • Peptide Fragments / chemistry
  • Peptide Fragments / metabolism
  • Peptides / chemistry*
  • Peptides / metabolism
  • Protein Multimerization
  • Proteomics / methods
  • Tissue Extracts / chemistry
  • Trefoil Factor-3


  • Cell Adhesion Molecules
  • FCGBP protein, human
  • Peptide Fragments
  • Peptides
  • TFF3 protein, human
  • Tissue Extracts
  • Trefoil Factor-3
  • Hydrogen Sulfide