Pancreatic spasmolytic polypeptide: first three-dimensional structure of a member of the mammalian trefoil family of peptides

Gajhede, Michael; Petersen, Thomas Nordahl; Henriksen, A.; Petersen, Jørn Henrik; Dauter, Zbigniew; Wilson, K.S.; Thim, Lars

doi:10.1016/0969-2126(93)90014-8

Cited by 61 publications

(88 citation statements)

References 29 publications

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“…It has been suggested that trefoil peptides in general, including ITF and pS2, may act to stabilise the mucous gel layer since they are coexpressed with mucin-type glycoproteins in the human gastrointestinal tract [23]. These mucins are covered by O-linked carbohydrates and preliminary modelling studies by us as well as by others [6] indicate that some of the surface pockets on each trefoil may bind carbohydrate units. Hence, trefoil domains may bind carbohydrate chains attached to mucins which under the right conditions, such as mucosal damage (ulceration, injury), the trefoils could form disulphide-linked dimers.…”

Section: Functional Implications Of Ps2 and Itf Dimerisationmentioning

confidence: 99%

Characterisation of the single copy trefoil peptides intestinal trefoil factor and pS2 and their ability to form covalent dimers

Chinery

Bates

et al. 1995

FEBS Letters

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A bacterial recombinant expression system was established to produce biologically active rat Intestinal Trefoil Factor (rITF). Characterisation of purified rITF shows that both monomers and dimers can be observed under reducing and non-reducing conditions, respectively. Site-directed mutagenesis studies show that Cys57 is necessary for rITF dimer formation. Samples of human gastrointestinal tissue following biopsy also demonstrated the presence of reducible human pS2 and ITF covalent dimers. Three-dimensional models for pS2 and ITF support the hypothesis that both pS2 and ITF can exist as disulphide-linked dimers in vivo and that any proposed function for these peptides must take dimer formation into account.

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Section: Functional Implications Of Ps2 and Itf Dimerisationmentioning

confidence: 99%

Characterisation of the single copy trefoil peptides intestinal trefoil factor and pS2 and their ability to form covalent dimers

Chinery

Bates

et al. 1995

FEBS Letters

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“…Furthermore, a seventh disulfide bridge links Cys 6 and Cys 104 ( Fig. 1) (8,9). This is probably the reason why TFF2 is stable in the gastric juice (4).…”

Section: Introductionmentioning

confidence: 99%

“…Thus, a lectin activity of TFF2 was predicted to be responsible for its non-covalent binding to MUC6, particularly to its characteristic structure GlcNAcα1→4Galβ1→R (12). Of note, based on its crystal structure a lectin activity cross-linking mucins have already been discussed for TFF2 (9). In particular, two hydrophobic clefts have been identified, one within each TFF domain, and all conserved residues are localized in their vicinity; two monosaccharides have been suggested to fit into each groove with the highly conserved Trp 45 and Trp 94 ( Fig.…”

Section: Tff2 and Its Function In The Gastric Mucus Barriermentioning

confidence: 99%

“…Neither is it known currently, if the fucosylated LacdiNAc structure is recognized by galectins, in particular by galectin-3. Interestingly, porcine pancreatic TFF2 forms non-covalently linked dimers in the solid phase (9,11) as well as in solution (12); the latter being unusually resistant even to boiling SDS (12). TFF2 is typically co-secreted with the mucin MUC6 from gastric fundic and antral glands (mucous neck and antral gland cells, respectively) as well as duodenal Brunner's glands (13)(14)(15)(16)(17) and represents a characteristic constituent of the gastroduodenal mucus (18).…”

Section: Tff2 a Muc6-binding Lectin Stabilizing The Gastric Mucus Bamentioning

confidence: 99%

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TFF2, a MUC6-binding lectin stabilizing the gastric mucus barrier and more (Review)

Hoffmann

2015

International Journal of Oncology

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Abstract. The peptide TFF2 (formerly 'spasmolytic polypeptide'), a member of the trefoil factor family (TFF) containing two TFF domains, is mainly expressed together with the mucin MUC6 in the gastric epithelium and duodenal Brunner's glands. Pathologically, TFF2 expression is observed ectopically during stone diseases, chronic inflammatory conditions and in several metaplastic and neoplastic epithelia; most prominent being the 'spasmolytic polypeptide-expressing metaplasia' (SPEM), which is an established gastric precancerous lesion. TFF2 plays a critical role in maintaining gastric mucosal integrity and appears to restrain tumorigenesis in the stomach. Recently, porcine TFF2 has been shown to interact with the gastric mucin MUC6 and thus stabilize the gastric mucus barrier. On the one hand, TFF2 binds to MUC6 via non-covalent lectin interactions with the glycotope GlcNAcα1→4Galβ1→R. On the other hand, TFF2 is probably also covalently bound to MUC6 via disulfide bridges. Thus, implications for the complex multimeric assembly, cross-linking, and packaging of MUC6 as well as the rheology of gastric mucus are discussed in detail in this review. Furthermore, TFF2 is also expressed in minor amounts in the immune and nervous systems. Thus, similar to galectins, its lectin activity would perfectly enable TFF2 to form multivalent complexes and cross-linked lattices with a plethora of transmembrane glycoproteins and thus modulate different signal transduction processes. This could explain the multiple and diverse biological effects of TFF2 [e.g., motogenic, (anti)apoptotic, and angiogenic effects]. Finally, a function during fertilization is also possible for TFF domains because they occur as shuffled modules in certain zona pellucida proteins.

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“…Beyond the characteristic cysteine patterns we found highly conserved positions in loop 2 (corresponding to the hTFF2 positions Ile47 and Thr48) and in loop 3 (corresponding to the hTFF2 positions Phe-108 and Trp-117). In particular the latter two aromatic residues were claimed to stabilize the fold of the domain and to play a role in protein binding (24).…”

Section: Wfa Affinity Chromatographic Enrichment Of Lacdinacpositive mentioning

confidence: 99%

Trefoil Factor Family Domains Represent Highly Efficient Conformational Determinants for N-Linked N,N′-di-N-acetyllactosediamine (LacdiNAc) Synthesis

Bonar

Hanisch

2014

Journal of Biological Chemistry

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Background: Absent microheterogeneity of LacdiNAc N-glycan on human gastric TFF2 points to high stringency control mechanism. Results: Single intact TFF domains of TFF2 control the ␤4-GalNAc transfer to terminal GlcNAc residues as conformational determinants. Conclusion:The role of a hydrophobic patch is hypothesized to form the essential part of the determinant. Significance: The restricted expression of LacdiNAc on extracellular matrix proteins relates to important biological processes.

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Pancreatic spasmolytic polypeptide: first three-dimensional structure of a member of the mammalian trefoil family of peptides

Cited by 61 publications

References 29 publications

Characterisation of the single copy trefoil peptides intestinal trefoil factor and pS2 and their ability to form covalent dimers

Characterisation of the single copy trefoil peptides intestinal trefoil factor and pS2 and their ability to form covalent dimers

TFF2, a MUC6-binding lectin stabilizing the gastric mucus barrier and more (Review)

Trefoil Factor Family Domains Represent Highly Efficient Conformational Determinants for N-Linked N,N′-di-N-acetyllactosediamine (LacdiNAc) Synthesis

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