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

Bonar, David; Hanisch, Franz‐Georg

doi:10.1074/jbc.m114.596049

Cited by 14 publications

(17 citation statements)

References 41 publications

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“…A lectin-like activity has also been reported for TFF1, which binds Helicobacter pylori lipopolysaccharide (LPS) in an α-glucosidase-sensitive manner 22 , and gastric mucin 23 . While unique protein-protein interactions may occur between the TFFs and their many reported binding partners 24 , a TFF lectin activity would also explain their association with such a diverse array of glycoproteins. However, at present, the lectin activity of each TFF remains poorly characterised.…”

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confidence: 99%

Trefoil factors share a lectin activity that defines their role in mucus

et al. 2020

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The mucosal epithelium secretes a host of protective disulfide-rich peptides, including the trefoil factors (TFFs). The TFFs increase the viscoelasticity of the mucosa and promote cell migration, though the molecular mechanisms underlying these functions have remained poorly defined. Here, we demonstrate that all TFFs are divalent lectins that recognise the GlcNAc-α-1,4-Gal disaccharide, which terminates some mucin-like O-glycans. Degradation of this disaccharide by a glycoside hydrolase abrogates TFF binding to mucins. Structural, mutagenic and biophysical data provide insights into how the TFFs recognise this disaccharide and rationalise their ability to modulate the physical properties of mucus across different pH ranges. These data reveal that TFF activity is dependent on the glycosylation state of mucosal glycoproteins and alludes to a lectin function for trefoil domains in other human proteins.

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Trefoil factors share a lectin activity that defines their role in mucus

et al. 2020

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“…Combined supernatants were dried by vacuum evaporation and depleted of borate by repeated addition of 50 µL of 1% acetic acid in methanol followed by nitrogen evaporation. N -glycans were released by PNGaseF-digestion of the tryptic peptides [ 22 ]. Permethylation of glycan chains was performed by sequential incubations of the dry samples with finely powdered NaOH in DMSO and methyliodide as described [ 23 ].…”

Section: Methodsmentioning

confidence: 99%

Functional Analysis of the Glucuronyltransferases GlcAT-P and GlcAT-S of Drosophila melanogaster: Distinct Activities towards the O-linked T-antigen

Breloy

Schwientek²,

Althoff

et al. 2016

Biomolecules

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The Drosophila melanogaster glucuronyltransferases dGlcAT-S and dGlcAT-P were reported to be expressed ubiquitously and results of in vitro activity assays indicate a functional redundancy. We analyzed both transferases in vivo and in vitro and could show significant differences in their activity towards N-and O-glycoproteins in vivo. While GlcAT-P is able to use N-linked N-acetyllactosamine chains and the O-linked T-antigen as a substrate to form non-sulfated HNK1- (GlcAβ1-3Galβ1-4GlcNAcβ1-) and glucuronyl-T-antigens in vivo, GlcAT-S adds glucuronic acid only to N-linked chains, thereby synthesizing only the non-sulfated HNK1-antigen.

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“…A unique feature of this small protein is the exposure of a hydrophobic patch lining a groove formed by loops 2 and 3 of the TFF domains ( Figure 1 A) [ 13 ]. This groove has been claimed to be responsible for protein–protein and protein–carbohydrate interactions [ 13 , 14 ]. Besides a series of hydrophobic amino acid residues, two sets of highly-conserved aromatic residues, Phe-59/Trp-68 in the P1 domain, and Phe-108/Trp-117 in the P2 domain, flank loop 3 ( Figure 1 A).…”

Section: The Lectin Domain Of H Tff2mentioning

confidence: 99%

The Double Face of Mucin-Type O-Glycans in Lectin-Mediated Infection and Immunity

2018

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Epithelial human blood group antigens (HBGAs) on O-glycans play roles in pathogen binding and the initiation of infection, while similar structures on secretory mucins exert protective functions. These double-faced features of O-glycans in infection and innate immunity are reviewed based on two instructive examples of bacterial and viral pathogens. Helicobacter pylori represents a class 1 carcinogen in the human stomach. By expressing blood group antigen-binding adhesin (BabA) and LabA adhesins that bind to Lewis-b and LacdiNAc, respectively, H. pylori colocalizes with the mucin MUC5AC in gastric surface epithelia, but not with MUC6, which is cosecreted with trefoil factor family 2 (TFF2) by deep gastric glands. Both components of the glandular secretome are concertedly up-regulated upon infection. While MUC6 expresses GlcNAc-capped glycans as natural antibiotics for H. pylori growth control, TFF2 may function as a probiotic lectin. In viral infection human noroviruses of the GII genogroup interact with HBGAs via their major capsid protein, VP1. HBGAs on human milk oligosaccharides (HMOs) may exert protective functions by binding to the P2 domain pocket on the capsid. We discuss structural details of the P2 carbohydrate-binding pocket in interaction with blood group H/Lewis-b HMOs and fucoidan-derived oligofucoses as effective interactors for the most prevalent norovirus strains, GII.4 and GII.17.

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

Cited by 14 publications

References 41 publications

Trefoil factors share a lectin activity that defines their role in mucus

Trefoil factors share a lectin activity that defines their role in mucus

Functional Analysis of the Glucuronyltransferases GlcAT-P and GlcAT-S of Drosophila melanogaster: Distinct Activities towards the O-linked T-antigen

The Double Face of Mucin-Type O-Glycans in Lectin-Mediated Infection and Immunity

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