Glycomarkers in parasitic infections and allergy

Hoffmann‐Sommergruber, Karin; Paschinger, Katharina; Wilson, Iain B. H.

doi:10.1042/bst0390360

Cited by 9 publications

(8 citation statements)

References 50 publications

(56 reference statements)

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“…The GlcNAcβ1,4[Fucα1,3]GlcNAc motif is also a central part of the anti-HRP epitope that it is recognized by antisera raised against HRP in agreement with the isolation of CCL2 as HRP-binding lectin (Figure 1A). Since this epitope is also a key carbohydrate determinant of pollen and insect venom allergens [46], it appears that the same glycoepitope has been selected as target by the antibody-mediated mammalian adaptive immune system and a lectin-mediated fungal defence system.…”

Section: Discussionmentioning

confidence: 99%

Plasticity of the β-Trefoil Protein Fold in the Recognition and Control of Invertebrate Predators and Parasites by a Fungal Defence System

et al. 2012

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Discrimination between self and non-self is a prerequisite for any defence mechanism; in innate defence, this discrimination is often mediated by lectins recognizing non-self carbohydrate structures and so relies on an arsenal of host lectins with different specificities towards target organism carbohydrate structures. Recently, cytoplasmic lectins isolated from fungal fruiting bodies have been shown to play a role in the defence of multicellular fungi against predators and parasites. Here, we present a novel fruiting body lectin, CCL2, from the ink cap mushroom Coprinopsis cinerea. We demonstrate the toxicity of the lectin towards Caenorhabditis elegans and Drosophila melanogaster and present its NMR solution structure in complex with the trisaccharide, GlcNAcβ1,4[Fucα1,3]GlcNAc, to which it binds with high specificity and affinity in vitro. The structure reveals that the monomeric CCL2 adopts a β-trefoil fold and recognizes the trisaccharide by a single, topologically novel carbohydrate-binding site. Site-directed mutagenesis of CCL2 and identification of C. elegans mutants resistant to this lectin show that its nematotoxicity is mediated by binding to α1,3-fucosylated N-glycan core structures of nematode glycoproteins; feeding with fluorescently labeled CCL2 demonstrates that these target glycoproteins localize to the C. elegans intestine. Since the identified glycoepitope is characteristic for invertebrates but absent from fungi, our data show that the defence function of fruiting body lectins is based on the specific recognition of non-self carbohydrate structures. The trisaccharide specifically recognized by CCL2 is a key carbohydrate determinant of pollen and insect venom allergens implying this particular glycoepitope is targeted by both fungal defence and mammalian immune systems. In summary, our results demonstrate how the plasticity of a common protein fold can contribute to the recognition and control of antagonists by an innate defence mechanism, whereby the monovalency of the lectin for its ligand implies a novel mechanism of lectin-mediated toxicity.

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Section: Discussionmentioning

confidence: 99%

Plasticity of the β-Trefoil Protein Fold in the Recognition and Control of Invertebrate Predators and Parasites by a Fungal Defence System

et al. 2012

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“…The first two categories contain the widely abundant Lewis‐type blood group antigens Le a , Le b , Le x , and Le y , as well as substituted versions thereof, including sialyl Le x (sLe x ) and several sulfated Le x , Le y , and sLe x epitopes. Glycans containing 3FChB are members of the third category that contain α1,3‐fucosylated N ‐glycan cores typically found in plants and invertebrates . Interestingly, several additional motifs that are usually not associated with Lewis antigens were found: α1,3‐fucosylated Lacdi N Ac (LDNF) present in helminths and sea squirt, species‐specific amphibian egg jelly coats with an α1,4‐fucosylation, and fucosylated chondroitin sulfate also display the downfield‐shifted H5 resonance of their Fuc moiety.…”

Section: Resultsmentioning

confidence: 99%

“…Glycansc ontaining 3FChB are members of the third category that contain a1,3-fucosylated N-glycan cores typically found in plants and invertebrates. [23] Interestingly,severaladditional motifs that are usually not associated with Lewis antigens were found: a1,3-fucosylated LacdiNAc (LDNF) present in helminths [24] and sea squirt, [25] species-specific amphibian egg jelly coats with an a1,4-fucosylation, [26] and fucosylated chondroitin sulfate [27] also display the downfield-shifted H5 resonance of their Fuc moiety.M oreover, Lewis-type-like antigensi nw hich the reducing end of GlcNAc Figure 2. Structuralmotifsd isplaying ac haracteristic 1 Hc hemical shift for Fuc H5.…”

Section: Statisticsofh 5c Hemical Shift Of Fucose Displayadiscrete CLmentioning

confidence: 99%

A Secondary Structural Element in a Wide Range of Fucosylated Glycoepitopes

Aeschbacher

Zierke

Smieško

et al. 2017

Chemistry A European J

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The increasing understanding of the essential role of carbohydrates in development, and in a wide range of diseases fuels a rapidly growing interest in the basic principles governing carbohydrate-protein interactions. A still heavily debated issue regarding the recognition process is the degree of flexibility or rigidity of oligosaccharides. Combining NMR structure determination based on extensive experimental data with DFT and database searches, we have identified a set of trisaccharide motifs with a similar conformation that is characterized by a non-conventional C-H⋅⋅⋅O hydrogen bond. These motifs are present in numerous classes of oligosaccharides, found in everything from bacteria to mammals, including Lewis blood group antigens but also unusual motifs from amphibians and marine invertebrates. The set of trisaccharide motifs can be summarized with the consensus motifs X-β1,4-[Fucα1,3]-Y and X-β1,3-[Fucα1,4]-Y-a secondary structure we name [3,4]F-branch. The wide spectrum of possible modifications of this scaffold points toward a large variety of glycoepitopes, which nature generated using the same underlying architecture.

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“…core α1,3 fucose). This non-mammalian epitope, found on plant and insect glycoproteins including pollen, food and venom allergens, is often a target of IgE in the sera of allergy patients (Paschinger et al, 2005a, Hoffmann-Sommergruber et al, 2011, Tretter et al, 1993). Furthermore, polyclonal antibodies raised against plant glycoproteins, especially horseradish peroxidase (HRP), have been extensively used to identify core α1,3-fucosylated and/or β1,2-xylosylated N-glycans in various non-vertebrate species.…”

Section: Introductionmentioning

confidence: 99%

The fucomic potential of mosquitoes: Fucosylated N-glycan epitopes and their cognate fucosyltransferases

Kurz

King

Dinglasan

et al. 2016

Insect Biochemistry and Molecular Biology

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Fucoconjugates are key mediators of protein-glycan interactions in prokaryotes and eukaryotes. As examples, N-glycans modified with the non-mammalian core α1,3-linked fucose have been detected in various organisms ranging from plants to insects and are immunogenic in mammals. The rabbit polyclonal antibody raised against plant horseradish peroxidase (anti-HRP) is able to recognize the α1,3-linked fucose epitope and is also known to specifically stain neural tissues in the fruit fly Drosophila melanogaster. In this study, we have detected and localized the anti-HRP cross-reactivity in another insect species, the malaria mosquito vector Anopheles gambiae. We were able to identify and structurally elucidate fucosylated N-glycans including core mono- and difucosylated structures (responsible for anti-HRP cross reactivity) as well as a Lewis-type antennal modification on mosquito anionic N-glycans by applying enzymatic and chemical treatments. The three mosquito fucosyltransferase open reading frames (FucT6, FucTA and FucTC) required for the in vivo biosynthesis of the fucosylated N-glycan epitopes were identified in the Anopheles gambiae genome, cloned and recombinantly expressed in Pichia pastoris. Using a robust MALDI-TOF MS approach, we characterised the activity of the three recombinant fucosyltransferases in vitro and demonstrate that they share similar enzymatic properties as compared to their homologues from D. melanogaster and Apis mellifera. Thus, not only do we confirm the neural reactivity of anti-HRP in a mosquito species, but also demonstrate enzymatic activity for all its α1,3- and α1,6-fucosyltransferase homologues, whose specificity matches the results of glycomic analyses.

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Glycomarkers in parasitic infections and allergy

Cited by 9 publications

References 50 publications

Plasticity of the β-Trefoil Protein Fold in the Recognition and Control of Invertebrate Predators and Parasites by a Fungal Defence System

Plasticity of the β-Trefoil Protein Fold in the Recognition and Control of Invertebrate Predators and Parasites by a Fungal Defence System

A Secondary Structural Element in a Wide Range of Fucosylated Glycoepitopes

The fucomic potential of mosquitoes: Fucosylated N-glycan epitopes and their cognate fucosyltransferases

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