Wu, A.M., Wu, J.H., Herp, A. & Liu, J-H. Effect of polyvalencies of glycotopes on the binding of a lectin from the edible mushroom, Agaricus bisporus. Biochem. J. 371, 311-320

Glyco-Immunochemistry Research Laboratory, Institute of Molecular and Cellular Biology, Chang-Gung University, Kwei-San, Tao-Yuan 333, Taiwan.
Biochemical Journal (Impact Factor: 4.4). 04/2003; 371(Pt 2):311-20. DOI: 10.1042/BJ20021361
Source: PubMed


Agaricus bisporus agglutinin (ABA) isolated from edible mushroom has a potent anti-proliferative effect on malignant colon cells with considerable therapeutic potential as an anti-neoplastic agent. Since previous studies on the structural requirement for binding were limited to molecular or submolecular levels of Galbeta1-3GalNAc (T; Thomsen-Friedenreich disaccharide glycotope; where Gal represents D-galactopyranose and GalNAc represents 2-acetamido-2-deoxy-D-galactopyranose) and its derivatives, the binding properties of ABA were further investigated using our collection of glycans by enzyme-linked lectinosorbent assay and lectin-glycan inhibition assay. The results indicate that polyvalent Galbeta1-related glycotopes, GalNAcalpha1-Ser/Thr (Tn), and their cryptoforms, are the most potent factor for ABA binding. They were up to 5.5x10(5) and 4.7x10(6) times more active than monomeric T and GalNAc respectively. The affinity of ABA for ligands can be ranked as: multivalent T (alpha) (Galbeta1-3GalNAcalpha1-), Tn and I / II (Galbeta1-3GlcNac/Galbeta1-4GlcNAc, where GlcNAc represents 2-acetamido-2-deoxy-D-glucopyranose)>monomeric T (alpha) and Tn > I >GalNAc> II, L (Galbeta1-4Glc, where Glc represents D-glucopyranose) and Gal (inactive). These specific binding features of ABA establish the importance of affinity enhancement by high-density polyvalent (versus multiantennary I / II) glycotopes and facilitate our understanding of the lectin receptor recognition events relevant to its biological activities.

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    • "The specificity and avidity of lectin–carbohydrate interactions are influenced by many factors such as structures, orientations, and density of ligands. Formation of a multivalent glycan complex can substantially affect the overall avidity of the interactions and selectivity of recognition [10], [19], [20]. In this context, a lectin microarray is a useful glycoanalytical tool that can also detect multivalency effects. "
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    ABSTRACT: Immunoglobulin A nephropathy (IgAN) is a form of chronic glomerulonephritis characterized by the deposition of IgA immune complexes in the glomerular region. The cause of IgAN is unknown, but multiple mechanisms have been suggested. We previously reported a rare case of mesangioproliferative glomerulonephritis in a patient with monoclonal immunoglobulin deposition disease associated with monoclonal IgA1. In this study, we performed the detailed analyses of serum IgA1 from this patient in comparison with those from patients with mIgA plasma cell disorder without renal involvement and healthy volunteers. We found unusual polymerization of IgA1 with additional N-glycosylation distinctive in this patient, which was different from known etiologies. Glycan profiling of IgA1 by the lectin microarray revealed an intense signal for Wisteria floribunda agglutinin (WFA). This signal was reduced by disrupting the native conformation of IgA1, suggesting that the distinct glycan profile was reflecting the conformational alteration of IgA1, including the glycan conformation detected as additional N-glycans on both the heavy and light chains. This unusually polymerized state of IgA1 would cause an increase of the binding avidity for lectins. WFA specifically recognized highly polymerized and glycosylated IgA1. Our results of analysis in the rare case of a patient with monoclonal immunoglobulin deposition disease suggest that the formation of unusually polymerized IgA1 is caused by divergent mechanisms including multiple structural alterations of glycans, which contributes to IgA1 deposition and mesangium proliferation.
    Full-text · Article · Mar 2014 · PLoS ONE
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    • "Combining previous and current results [5] [6] [7], it is proposed that: (a) the combining site of ABA is composed of one major site a potent –OH configuration of GalNAc and a weak –OH configuration of GlcNAc i.e. GalNAc ) GlcNAc and two subsites (Galb1-3/4) at non-reducing end for fitting four different intensities of glycotopes and three recognition systems (Tn, T a and "
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    ABSTRACT: For the GalNAcalpha1--> specific Agaricus bisporus agglutinin (ABA) from an edible mushroom, the mechanism of polyvalent Galbeta1-->3/4GlcNAcbeta1--> complex in ABA-carbohydrate recognition has not been well defined since Gal and GlcNAc are weak ligands. By enzyme-linked lectinosorbent and inhibition assays, we show that the polyvalent Galbeta1-->3/4GlcNAcbeta1--> in natural glycans also play vital roles in binding and we propose that four different intensities of glycotopes (Galbeta1-3GalNAcalpha1-, GalNAcalpha1-Ser/Thr and Galbeta1-3/4GlcNAcbeta1-) construct three recognition systems at the same domain. This peculiar concept provides the most comprehensive mechanism for the attachment of ABA to target glycans and malignant cells at the molecular level.
    Preview · Article · Aug 2010 · FEBS letters
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    • "n in the PA assay strongly indicates that the presence of high - density polyvalent glycotopes strongly enhances the affinity of the lectin . Both the identity of the reactive glycans and the appar - ent preferential binding to multivalent epitopes indi - cate that the M . polymorpha lectin closely resembles ABA for what concerns its specificity ( Wu et al . , 2003 ) ."
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    ABSTRACT: A lectin different from the previously described mannose-binding agglutinins has been isolated from the liverwort Marchantia polymorpha. Biochemical characterization of the purified lectin combined with the data from earlier transcriptome analyses demonstrated that the novel M. polymorpha agglutinin is not related to any of the known plant lectin families, but closely resembles the Agaricus bisporus-type lectins, which hitherto have been found exclusively in fungi. Immunolocalization studies confirmed that lectin is exclusively associated with plant cells, ruling out the possibility of a fungal origin. Extensive screening of publicly accessible databases confirmed that, apart from fungi, the occurrence of A. bisporus-type lectins is confined to M. polymorpha and the moss Tortula ruralis. Expression of a typical fungal protein in a liverwort and a moss raises the question of the origin of the corresponding genes. Regardless of the evolutionary origin, the presence of a functional A. bisporus lectin ortholog in M. polymorpha provides evidence for the expression of an additional carbohydrate-binding domain in Viridiplantae.
    Full-text · Article · Jul 2007 · Plant physiology
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