Different Forms of TFF3 in the Human Saliva: Heterodimerization with IgG Fc Binding Protein (FCGBP)

Abstract

The peptide TFF3 is a member of a family of secretory lectins, and is typically synthesized by mucous epithelia together with mucins. It is mainly released from intestinal goblet cells as a high-molecular mass heterodimer with IgG Fc binding protein (FCGBP). Herein, we investigated human saliva by fast protein liquid chromatography (FPLC) and proteomics and identified high- and low-molecular-mass forms of TFF3. Whereas the high-molecular-mass forms represent a heterodimer with FCGBP, the low-molecular-mass forms represent homodimeric TFF3 forms. Proteomic analysis also revealed a C-terminally truncated form of TFF3. We hypothesize that salivary TFF3-FCGBP might play a role in the innate immune defense of the oral cavity and that TFF3 might also bind to microbial glycans. The known interaction of TFF3 with the agglutinin DMBT-1, a typical constituent of human saliva, further supports this protective role.

Molecular Alterations in the Stomach of Tff1-Deficient Mice: Early Steps in Antral Carcinogenesis

“…This is in line with the observation that FCGBP is the highest upregulated early defense gene in fish skin after microbial infection [61]. The formation of a Tff1-Fcgbp heterodimer in the gastric mucosa is not really surprising because the overall structures of Tff1 and Tff3 are similar; the latter is already known to form disulfide-linked TFF3-FCGBP heterodimers in the human intestine and saliva [30,31].…”

“…Furthermore, when monomeric Tff1 (region 1) was eluted and analyzed again, a double band was detected ( Figure 2F). Thus, Tff1 also exists in a shortened form maybe similar as shown for human TFF3 recently [31]. This shortened form is also visible in Figure 2A.…”

“…In the past, in both the human intestine and saliva TFF3 has been found to form a disulfide-linked heterodimer with FCGBP [30,31]. As TFF1 and FCGBP are both secretory products of gastric surface mucous cells and the overall structure of TFF1 and TFF3 is very similar including the occurrence of seven cysteine residues, we tested whether Tff1 forms a complex with Fcgbp in the murine stomach.…”

The Tumor Suppressor TFF1 Occurs in Different Forms and Interacts with Multiple Partners in the Human Gastric Mucus Barrier: Indications for Diverse Protective Functions

“…Of special note, multiple copies of this motif are present in FCGBP and this protein has already been proposed to play a role in the dimerization of TFF3, which has an analogous structure to TFF1 [45]. This mechanism is of particular interest since FCGBP forms heterodimers with TFF1 and TFF3 [40,45,46].…”

“…The existence of a TFF1-FCGBP heterodimer in the stomach was not surprising because both TFF1 and FCGBP are secretory products of gastric surface mucous cells and both contain an odd number of cysteine residues [6,51,73]. Furthermore, FCGBP also forms a heterodimer with TFF3, which has an analogous structure like TFF1, including the seventh cysteine residue outside the TFF domain [45,46]. However, the relative amount of TFF3-FCGBP is much higher than that of TFF1-FCGBP.…”