Human Intestinal TFF3 Forms Disulfide-Linked Heteromers with the Mucus-Associated FCGBP Protein and Is Released by Hydrogen Sulfide
- 12 May 2010
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of Proteome Research
- Vol. 9 (6), 3108-3117
- https://doi.org/10.1021/pr100020c
Abstract
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).Keywords
This publication has 65 references indexed in Scilit:
- The protein disulfide isomerase AGR2 is essential for production of intestinal mucusProceedings of the National Academy of Sciences of the United States of America, 2009
- XBP1 Links ER Stress to Intestinal Inflammation and Confers Genetic Risk for Human Inflammatory Bowel DiseaseCell, 2008
- Aberrant Mucin Assembly in Mice Causes Endoplasmic Reticulum Stress and Spontaneous Inflammation Resembling Ulcerative ColitisPLoS Medicine, 2008
- IL-13 and Epidermal Growth Factor Receptor Have Critical but Distinct Roles in Epithelial Cell Mucin ProductionAmerican Journal of Respiratory Cell and Molecular Biology, 2007
- Localization of TFF3 peptide in human esophageal submucosal glands and gastric cardia: differentiation of two types of gastric pit cells along the rostro-caudal axisCell and tissue research, 2007
- Cleavage in the GDPH sequence of the C-terminal cysteine-rich part of the human MUC5AC mucinBiochemical Journal, 2006
- Trefoil factor family (TFF) peptides of normal human Vater’s ampullaCell and tissue research, 2005
- A gradient of TFF3 (trefoil factor family 3) peptide synthesis within the normal human gastric mucosaCell and tissue research, 2004
- Trefoil factors: initiators of mucosal healingNature Reviews Molecular Cell Biology, 2003
- Expression of spasmolysin (FIM-A.1): An integumentary mucin from Xenopus laevisExperimental Cell Research, 1990