Human Intestinal TFF3 Forms Disulfide-Linked Heteromers with the Mucus-Associated FCGBP Protein and Is Released by Hydrogen Sulfide
Human Intestinal TFF3 Forms Disulfide-Linked Heteromers with the Mucus-Associated FCGBP Protein and Is Released by Hydrogen Sulfide
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DOI：
10.1021/pr100020c
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发表时间：
2010-06-01
影响因子：
4.4
通讯作者：
Hoffmann, Werner
中科院分区：
文献类型：
--
作者：
Albert, Timo K.;Laubinger, Werner;Hoffmann, Werner
TFF 3是属于三叶因子家族的分泌肽，预测大小为59个氨基酸残基，含有7个半胱氨酸残基。它主要在肠杯状细胞中表达，在粘膜再生和修复过程中起关键作用。在这些研究过程中，显示人结肠TFF 3主要作为高分子量异聚体存在。该异聚体的纯化和通过LC-ESI-MS/MS分析的表征将IgG Fc结合蛋白（FCGBP）鉴定为TFF 3的二硫键连接的伴侣蛋白。FCGBP是由杯状细胞分泌的肠粘液的成分。此外，在人结肠提取物中检测到少量的TFF 3/单体和仅少量的TFF 3/二聚体。在这里，我们表明，这些TFF 3形式可以释放从纯化的TFF 3-FCGBP异聚体复合物在体外用硫化氢（H（2）S）还原。这种机制与报道的结肠腔中H（2）S浓度高的现象相一致。特别值得注意的是，这表明肠粘液是生物活性肽的储存库。还观察到FCGBP的蛋白水解加工，这与Johansson等人早先提出的多重自催化裂解一致（J. Proteome Res.2009，8，3549-3557）。
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).