Publications
413 results found
Liu Y, Lai L, Bumstead J, et al., 2011, The Role of Sialyl Glycan Recognition in Host Tissue Tropism of the Avian Parasite Eimeria tenella, PLoS Pathog, Vol: 7
Eimeria spp. are a highly successful group of intracellular protozoan parasites that develop within intestinal epithelial cells of poultry, causing coccidiosis. As a result of resistance against anticoccidial drugs and the expense of manufacturing live vaccines, it is necessary to understand the relationship between Eimeria and its host more deeply, with a view to developing recombinant vaccines. Eimeria possesses a family of microneme lectins (MICs) that contain microneme adhesive repeat regions (MARR). We show that the major MARR protein from Eimeria tenella, EtMIC3, is deployed at the parasite-host interface during the early stages of invasion. EtMIC3 consists of seven tandem MAR1-type domains, which possess a high specificity for sialylated glycans as shown by cell-based assays and carbohydrate microarray analyses. The restricted tissue staining pattern observed for EtMIC3 in the chicken caecal epithelium indicates that EtMIC3 contributes to guiding the parasite to the site of invasion in the chicken gut. The microarray analyses also reveal a lack of recognition of glycan sequences terminating in the N-glycolyl form of sialic acid by EtMIC3. Thus the parasite is well adapted to the avian host which lacks N-glycolyl neuraminic acid. We provide new structural insight into the MAR1 family of domains and reveal the atomic resolution basis for the sialic acid-based carbohydrate recognition. Finally, a preliminary chicken immunization trial provides evidence that recombinant EtMIC3 protein and EtMIC3 DNA are effective vaccine candidates
Haltiwanger RS, Feizi T, 2011, Glycobiology: the study of the sweet life, CURRENT OPINION IN STRUCTURAL BIOLOGY, Vol: 21, Pages: 573-575, ISSN: 0959-440X
- Author Web Link
- Cite
- Citations: 1
Capodicasa C, Chiani P, Bromuro C, et al., 2011, Plant production of anti-beta-glucan antibodies for immunotherapy of fungal infections in humans, Plant Biotechnol.J., Vol: 9, Pages: 776-787
There is an increasing interest in the development of therapeutic antibodies (Ab) to improve the control of fungal pathogens, but none of these reagents is available for clinical use. We previously described a murine monoclonal antibody (mAb 2G8) targeting beta-glucan, a cell wall polysaccharide common to most pathogenic fungi, which conferred significant protection against Candida albicans, Aspergillus fumigatus and Cryptococcus neoformans in animal models. Transfer of this wide-spectrum, antifungal mAb into the clinical setting would allow the control of most frequent fungal infections in many different categories of patients. To this aim, two chimeric mouse-human Ab derivatives from mAb 2G8, in the format of complete IgG or scFv-Fc, were generated, transiently expressed in Nicotiana benthamiana plants and purified from leaves with high yields (approximately 50 mg Ab/kg of plant tissues). Both recombinant Abs fully retained the beta-glucan-binding specificity and the antifungal activities of the cognate murine mAb against C. albicans. In fact, they recognized preferentially beta1,3-linked glucan molecules present at the fungal cell surface and directly inhibited the growth of C. albicans and its adhesion to human epithelial cells in vitro. In addition, both the IgG and the scFv-Fc promoted C. albicans killing by isolated, human polymorphonuclear neutrophils in ex vivo assays and conferred significant antifungal protection in animal models of systemic or vulvovaginal C. albicans infection. These recombinant Abs represent valuable molecules for developing novel, plant-derived immunotherapeutics against candidiasis and, possibly, other fungal diseases
Redelinghuys P, Antonopoulos A, Liu Y, et al., 2011, Early murine T-lymphocyte activation is accompanied by a switch from N-glycolyl- to N-acetyl-neuraminic acid and generation of ligands for siglec-E, J.Biol.Chem., Vol: 286, Pages: 34522-34532
It is well established that murine T-lymphocyte activation is accompanied by major changes in cell-surface sialylation, potentially influencing interactions with sialic acid-binding immunoglobulin-like lectins (siglecs). In the present study, we analysed early activation of murine CD4+ and CD8+ T-lymphocytes at 24 h. We observed a striking and selective up-regulation in the binding of a recombinant soluble form of siglec E, an inhibitory siglec which is expressed on several myeloid cell types including antigen presenting dendritic cells. In contrast, much lower levels of T cell binding were observed with other siglecs, including sialoadhesin, CD22, and siglec-F and the plant lectins Maackia amurensis leukoagglutinin and Sambucus nigra agglutinin. By mass spectrometry, the sialic acid content of 24-h-activated CD4+ and CD8+ T-lymphocytes exhibited an increased proportion of N-acetyl-neuraminic acid (NeuAc) to N glycolyl-neuraminic acid (NeuGc) in N-glycans. Reduced levels of NeuGc on the surface of activated T cells were demonstrated using an antibody specific for NeuGc and the expression levels of the gene encoding NeuAc to NeuGc converting enzyme, CMP-NeuAc hydroxylase, were also reduced. Siglec-E bound a wide range of sialylated structures in glycan arrays, had a preference for NeuAc versus NeuGc-terminated sequences and could recognise a set of sialoglycoproteins that included CD45, in lysates from activated T-lymphocytes. Collectively, these results show that early in T cell activation, glycan remodelling involves a switch from NeuGc- to NeuAc-terminating oligosaccharides on cell surface glycoproteins. This is associated with a strong up-regulation of siglec-E ligands which may be important in promoting cellular interactions between early-activated T-lymphocytes and myeloid cells expressing this inhibitory receptor
Feizi T, Liu Y, Palma AS, 2011, Bacterial, Fungal, and Algal Lectins: Combatants in Tug of War against HIV, Structure., Vol: 19, Pages: 1035-1037
High-resolution X-ray crystallography and NMR studies by Koharudin and Gronenborn in this issue provide new information on the mode of N-glycan recognition by a cyanobacterial agglutinin, with anti-HIV activity pointing to the pentamannosyl core as a novel target for therapeutic intervention
Watson AA, Lebedev AA, Hall BA, et al., 2011, Structural flexibility of the macrophage dengue virus receptor CLEC5A: implications for ligand binding and signaling, J.Biol.Chem., Vol: 286, Pages: 24208-24218
The human C-type lectin-like molecule CLEC5A is a critical macrophage receptor for dengue virus. The binding of dengue virus to CLEC5A triggers signaling through the associated adapter molecule DAP12, stimulating proinflammatory cytokine release. We have crystallized an informative ensemble of CLEC5A structural conformers at 1.9-A resolution and demonstrate how an on-off extension to a beta-sheet acts as a binary switch regulating the flexibility of the molecule. This structural information together with molecular dynamics simulations suggests a mechanism whereby extracellular events may be transmitted through the membrane and influence DAP12 signaling. We demonstrate that CLEC5A is homodimeric at the cell surface and binds to dengue virus serotypes 1-4. We used blotting experiments, surface analyses, glycan microarray, and docking studies to investigate the ligand binding potential of CLEC5A with particular respect to dengue virus. This study provides a rational foundation for understanding the dengue virus-macrophage interaction and the role of CLEC5A in dengue virus-induced lethal disease
Mollegaard KM, Duus K, Traeholt SD, et al., 2011, The interactions of calreticulin with immunoglobulin G and immunoglobulin Y, Biochim.Biophys.Acta, Vol: 1814, Pages: 889-899
Calreticulin is a chaperone of the endoplasmic reticulum (ER) assisting proteins in achieving the correctly folded structure. Details of the binding specificity of calreticulin are still a matter of debate. Calreticulin has been described as an oligosaccharide-binding chaperone but data are also accumulating in support of calreticulin as a polypeptide binding chaperone. In contrast to mammalian immunoglobulin G (IgG), which has complex type N-glycans, chicken immunoglobulin Y (IgY) possesses a monoglucosylated high mannose N-linked glycan, which is a ligand for calreticulin. Here, we have used solid and solution-phase assays to analyze the in vitro binding of calreticulin, purified from human placenta, to human IgG and chicken IgY in order to compare the interactions. In addition, peptides from the respective immunoglobulins were included to further probe the binding specificity of calreticulin. The experiments demonstrate the ability of calreticulin to bind to denatured forms of both IgG and IgY regardless of the glycosylation state of the proteins. Furthermore, calreticulin exhibits binding to peptides (glycosylated and non-glycosylated) derived from trypsin digestion of both immunoglobulins. Additionally, calreticulin peptide binding was examined with synthetic peptides covering the IgG Cgamma2 domain demonstrating interaction with approximately half the peptides. Our results show that the dominant binding activity of calreticulin in vitro is toward the polypeptide moieties of IgG and IgY even in the presence of the monoglucosylated high mannose N-linked oligosaccharide on IgY
Palma AS, Liu Y, Childs RA, et al., 2011, The human epithelial carcinoma antigen recognized by monoclonal antibody AE3 is expressed on a sulfoglycolipid in addition to neoplastic mucins, Biochem.Biophys.Res.Commun., Vol: 408, Pages: 548-552
The term human epithelial carcinoma antigen (HCA) has been applied collectively to mucin-type high molecular weight (>1000kDa) glycoproteins that are over-expressed in epithelial cancers. Since the 1990s, over 40 monoclonal antibodies have been raised that recognize HCA. There has been evidence that the antigenic determinants are mostly carbohydrates, but details have been elusive. Here we have carried out carbohydrate microarray analyses of one of the monoclonal antibodies, AE3, that has been regarded the 'most carcinoma specific' in respect to its ability to detect HCA in sera of patients with epithelial cancers. The microarrays encompassed a series of 492 sequence-defined glycan probes in the form of glycolipids and neoglycolipids. We have thus established that the antigen recognized by antibody AE3 is a carbohydrate sequence distinct from the A, B, H, Lewis(a/b), Lewis(x/y) and T antigens, but that it is strongly expressed on the monosulfated tetra-glycosyl ceramide, SM1a, Galbeta1-3GalNAcbeta1-4(3-O-sulfate)Galbeta1-4GlcCer. This is the first report of an anti-HCA to be characterized with respect to its recognition sequence and of the occurrence of the antigen on a glycolipid as well as on glycoproteins. Knowledge of a discrete glycan sequence as target antigen now opens the way to its exploration as a serologic cancer biomarker, namely to determine if the antigen elicits an autoantibody response in early non-metastatic cancer, or if it is shed and immunochemically detectable in more advanced disease
Otto DME, Campanero-Rhodes MA, Karamanska R, et al., 2011, An expression system for screening of proteins for glycan and protein interactions, ANALYTICAL BIOCHEMISTRY, Vol: 411, Pages: 261-270, ISSN: 0003-2697
- Author Web Link
- Cite
- Citations: 12
Palma A, Liu Y, Muhle-Goll C, et al., 2010, Neoglycolipid (NGL)-Based Microarrays Toward Defining the Recognition Sequence for Malectin: An ER-Resident Potential Regulator of <i>N</i>-Glycan Processing, Annual Conference of the Society-for-Glycobiology, Publisher: OXFORD UNIV PRESS INC, Pages: 1510-1511, ISSN: 0959-6658
Childs R, Liu Y, Palma A, et al., 2010, Observations on Receptor-Binding by Influenza Viruses using the Neoglycolipid (NGL)-Based Carbohydrate Microarray System, Annual Conference of the Society-for-Glycobiology, Publisher: OXFORD UNIV PRESS INC, Pages: 1529-1529, ISSN: 0959-6658
Liu Y, Childs RA, Matrosovich T, et al., 2010, Altered receptor specificity and cell tropism of D222G hemagglutinin mutants isolated from fatal cases of pandemic A(H1N1) 2009 influenza virus, J.Virol., Vol: 84, Pages: 12069-12074
Mutations in the receptor-binding site of the hemagglutinin of pandemic influenza A(H1N1) 2009 viruses have been detected sporadically. An Asp222Gly (D222G) substitution has been associated with severe or fatal disease. Here we show that 222G variants infected a higher proportion of ciliated cells in cultures of human airway epithelium than did viruses with 222D or 222E, which targeted mainly nonciliated cells. Carbohydrate microarray analyses showed that 222G variants bind a broader range of alpha2-3-linked sialyl receptor sequences of a type expressed on ciliated bronchial epithelial cells and on epithelia within the lung. These features of 222G mutants may contribute to exacerbation of disease
Hiruma-Shimizu K, Hosoguchi K, Liu Y, et al., 2010, Chemical synthesis, folding, and structural insights into O-fucosylated epidermal growth factor-like repeat 12 of mouse Notch-1 receptor, J.Am.Chem.Soc., Vol: 132, Pages: 14857-14865
Notch receptors are cell surface glycoproteins that play key roles in a number of developmental cascades in metazoa. The extracellular domains of Notch-1 receptors are composed of 36 tandem epidermal growth factor (EGF)-like repeats, many of which are modified at highly conserved consensus sites by an unusual form of O-glycan, with O-fucose. The O-fucose residues on certain EGF repeats may be elongated. In mammalian cells this can be a tetrasaccharide, Siaalpha2,3Galbeta1,4GlcNAcbeta1,3Fucalpha1-->. This elongation process is initiated by the action of O-fucose-specific beta1,3 N-acetylglucosaminyltransferases of the Fringe family. There is evidence that the addition of GlcNAc by Fringe serves as an essential modulator of the interaction of Notch with its ligands and the triggering of activation. Here we describe the efficient synthesis, folding, and structural characterization of EGF repeat 12 (EGF 12) of a mouse Notch-1 receptor bearing different O-fucose glycan chains. We demonstrate that the three disulfide bonds, Cys(456)-Cys(467) (C1-C3), Cys(461)-Cys(476) (C2-C4), and Cys(478)-Cys(487) (C5-C6) were correctly formed in the nonglycosylated as well as the O-fucosylated forms of EGF 12. Three-dimensional structural studies by NMR reveal that the methyl group of fucose is in close contact with ILe(475), Met(477), Pro(478) residues and this stabilizes the conformation of the antiparallel beta-sheet of EGF 12. The addition of the GlcNAc residue on O-fucosylated EGF 12 induces a significant conformational change in the adjacent tripeptide sequence, Gln(462)Asn(463)Asp(464), which is a motif involved in the natural, enzymatic O-fucosylation at the conserved site (Cys(461)X(4)Ser/ThrCys(467))
Neu U, Maginnis MS, Palma AS, et al., 2010, Structure-Function Analysis of the Human JC Polyomavirus Establishes the LSTc Pentasaccharide as a Functional Receptor Motif, CELL HOST & MICROBE, Vol: 8, Pages: 309-319, ISSN: 1931-3128
- Author Web Link
- Cite
- Citations: 146
Dunlop DC, Bonomelli C, Mansab F, et al., 2010, Polysaccharide mimicry of the epitope of the broadly neutralizing anti-HIV antibody, 2G12, induces enhanced antibody responses to self oligomannose glycans, GLYCOBIOLOGY, Vol: 20, Pages: 812-823, ISSN: 0959-6658
- Author Web Link
- Cite
- Citations: 60
O'Callaghan C, Anita M, Dunbar R, et al., 2010, Identification of glycolipid ligands for human MINCLE., JOURNAL OF IMMUNOLOGY, Vol: 184, ISSN: 0022-1767
Childs RA, Palma AS, Wharton S, et al., 2010, Receptor-binding specificity of pandemic influenza A (H1N1) 2009 virus determined by carbohydrate microarray (vol 27, pg 797, 2009), NATURE BIOTECHNOLOGY, Vol: 28, Pages: 178-178, ISSN: 1087-0156
- Author Web Link
- Cite
- Citations: 2
Friedrich N, Santos JM, Liu Y, et al., 2010, Members of a novel protein family containing microneme adhesive repeat domains act as sialic acid-binding lectins during host cell invasion by apicomplexan parasites, J.Biol.Chem., Vol: 285, Pages: 2064-2076
Numerous intracellular pathogens exploit cell surface glycoconjugates for host cell recognition and entry. Unlike bacteria and viruses, Toxoplasma gondii and other parasites of the phylum Apicomplexa actively invade host cells, and this process critically depends on adhesins (microneme proteins) released onto the parasite surface from intracellular organelles called micronemes (MIC). The microneme adhesive repeat (MAR) domain of T. gondii MIC1 (TgMIC1) recognizes sialic acid (Sia), a key determinant on the host cell surface for invasion by this pathogen. By complementation and invasion assays, we demonstrate that TgMIC1 is one important player in Sia-dependent invasion and that another novel Sia-binding lectin, designated TgMIC13, is also involved. Using BLAST searches, we identify a family of MAR-containing proteins in enteroparasitic coccidians, a subclass of apicomplexans, including T. gondii, suggesting that all these parasites exploit sialylated glycoconjugates on host cells as determinants for enteric invasion. Furthermore, this protein family might provide a basis for the broad host cell range observed for coccidians that form tissue cysts during chronic infection. Carbohydrate microarray analyses, corroborated by structural considerations, show that TgMIC13, TgMIC1, and its homologue Neospora caninum MIC1 (NcMIC1) share a preference for alpha2-3- over alpha2-6-linked sialyl-N-acetyllactosamine sequences. However, the three lectins also display differences in binding preferences. Intense binding of TgMIC13 to alpha2-9-linked disialyl sequence reported on embryonal cells and relatively strong binding to 4-O-acetylated-Sia found on gut epithelium and binding of NcMIC1 to 6'sulfo-sialyl Lewis(x) might have implications for tissue tropism
Ewers H, Römer W, Smith AE, et al., 2010, SV40 Binding to Its Receptor, GM1, Induces Membrane Invagination, Tubulation, and Infection, Nature Cell Biol, Vol: 12, Pages: 11-18
Palma AS, Liu Y, Muhle-Goll C, et al., 2010, Multifaceted approaches including neoglycolipid oligosaccharide microarrays to ligand discovery for malectin, Methods Enzymol., Vol: 478, Pages: 265-286
In this chapter, we describe the key procedures for isolation of the oligosaccharides and the preparation of neoglycolipid probes together with expression of malectin that have enabled the discovery of the highly selective binding of this newly described protein in the endoplasmic reticulum (ER) to a diglucosyl high-mannose N-glycan. This is the first indication of a bioactivity for a diglucosyl high-mannose N-glycan of the type that occurs in the ER of eukaryotic cells and which is an intermediate in the early steps of the N-glycosylation pathway of nascent proteins. The malectin story is an example of a powerful convergence of disciplines in biological sciences: (i) developmental biology, (ii) bioinformatics, (iii) recombinant protein expression, (iv) protein structural studies, (v) glucan biochemistry, and (vi) drug-assisted engineering of oligosaccharide biosynthesis, culminating in (vii) oligosaccharide "designer" microarrays, to clinch the remarkable selectivity of the binding of this newly discovered ER protein. Thus, the way is open to the identification of the role of malectin in the N-glycosylation pathway
Liu Y, Palma AS, Chai W, et al., 2009, The Latest on Malectin - A Lectin of the Endoplasmic Reticulum, Annual Meeting of the Society-for-Glycobiology, Publisher: OXFORD UNIV PRESS INC, Pages: 1301-1302, ISSN: 0959-6658
Allman SA, Jensen HH, Vijayakrishnan B, et al., 2009, Potent fluoro-oligosaccharide probes of adhesion in Toxoplasmosis, Chembiochem., Vol: 10, Pages: 2522-2529
Unnatural, NMR- and MRI-active fluorinated sugar probes, designed and synthesised to bind to the pathogenic protein TgMIC1 from Toxoplasma gondii, were found to display binding potency equal to and above that of the natural ligand. Dissection of the binding mechanism and modes, including the first X-ray crystal structures of a fluoro-oligosaccharide bound to a lectin, demonstrate that it is possible to create effective fluorinated probe ligands for the study of, and perhaps intervention in, sugar-protein binding events
Childs RA, Palma AS, Wharton S, et al., 2009, Receptor-binding specificity of pandemic influenza A (H1N1) 2009 virus determined by carbohydrate microarray, Nat.Biotechnol., Vol: 27, Pages: 797-799
Liu Y, Garnett JA, Leon E, et al., 2009, Detailed insights from microarray and crystallographic studies into carbohydrate recognition by microneme protein 1 (MIC1) of Toxoplasma gondii, Protein Sci., Vol: 18, Pages: 1935-1947
The intracellular protozoan Toxoplasma gondii is among the most widespread parasites. The broad host cell range of the parasite can be explained by carbohydrate microarray screening analyses that have demonstrated the ability of the T. gondii adhesive protein, TgMIC1, to bind to a wide spectrum of sialyl oligosaccharide ligands. Here, we investigate by further microarray analyses in a dose-response format the differential binding of TgMIC1 to 2-3- and 2-6-linked sialyl carbohydrates. Interestingly, two novel synthetic fluorinated analogs of 3'SiaLacNAc(1-4) and 3'SiaLacNAc(1-3) were identified as highly potent ligands. To understand the structural basis of the carbohydrate binding specificity of TgMIC1, we have determined the crystal structures of TgMIC1 micronemal adhesive repeat (MAR)-region (TgMIC1-MARR) in complex with five sialyl-N-acetyllactosamine analogs. These crystal structures have revealed a specific, water-mediated hydrogen bond network that accounts for the preferential binding of TgMIC1-MARR to arrayed 2-3-linked sialyl oligosaccharides and the high potency of the fluorinated analogs. Furthermore, we provide strong evidence for the first observation of a C--F...H--O hydrogen bond within a lectin-carbohydrate complex. Finally, detailed comparison with other oligosaccharide-protein complexes in the Protein Data Bank (PDB) reveals a new family of sialic-acid binding sites from lectins in parasites, bacteria, and viruses
Liu Y, Palma AS, Feizi T, 2009, Carbohydrate microarrays: key developments in glycobiology, Biol.Chem., Vol: 390, Pages: 647-656
Carbohydrate chains of glycoproteins, glycolipids, proteoglycans, and polysaccharides mediate processes of biological and medical importance through their interactions with complementary proteins. The unraveling of these interactions is therefore a priority in biomedical sciences. Carbohydrate microarray technology is a new development at the frontier of glycomics that is revolutionizing the study of carbohydrate-protein interactions and the elucidation of their specificities in endogenous biological processes, microbe-host interactions, and immune defense mechanisms. In this review, we briefly refer to the principles of numerous platforms since the introduction of carbohydrate microarrays in 2002, and we highlight platforms that are beyond proof-of-concept and have provided new biological information
Bleckmann C, Geyer H, Lieberoth A, et al., 2009, O-glycosylation pattern of CD24 from mouse brain, Biol.Chem., Vol: 390, Pages: 627-645
The cell adhesion molecule CD24 is a highly glycosylated glycoprotein that plays important roles in the central nervous system, the immune system and in tumor biology. Since CD24 comprises only a short protein core of approximately 30 amino acids and low conservation among species, it has been proposed that the functions of CD24 are mediated by its glycosylation pattern. Our present study provides evidence that interaction of CD24 with the cell adhesion molecule L1 is mediated by O-linked glycans carrying alpha2,3-linked sialic acid. Furthermore, de-N-glycosylated CD24 was shown to promote or inhibit neurite outgrowth of cerebellar neurons or dorsal root ganglion neurons, respectively, to the same extent as untreated CD24. Therefore, this study is focused on the structural elucidation of the chemically released, permethylated CD24 O-glycans by electrospray ionization ion trap mass spectrometry. Our analyses revealed the occurrence of a diverse mixture of mucin-type and O-mannosyl glycans carrying, in part, functionally relevant epitopes, such as 3-linked sialic acid, disialyl motifs, Le(X), sialyl-Le(X) or HNK-1 units. Hence, our data provide the basis for further studies on the contribution of carbohydrate determinants to CD24-mediated biological activities
Torosantucci A, Chiani P, Bromuro C, et al., 2009, Protection by anti-beta-glucan antibodies is associated with restricted beta-1,3 glucan binding specificity and inhibition of fungal growth and adherence., PLoS One, Vol: 4
Anti-β-glucan antibodies elicited by a laminarin-conjugate vaccine confer cross-protection to mice challenged with major fungal pathogens such as Candida albicans, Aspergillus fumigatus and Cryptococcus neoformans. To gain insights into protective β-glucan epitope(s) and protection mechanisms, we studied two anti-β-glucan monoclonal antibodies (mAb) with identical complementarity-determining regions but different isotypes (mAb 2G8, IgG2b and mAb 1E12, IgM). C. albicans, the most relevant fungal pathogen for humans, was used as a model. Both mAbs bound to fungal cell surface and to the β1,3-β1,6 glucan of the fungal cell wall skeleton, as shown by immunofluorescence, electron-microscopy and ELISA. They were also equally unable to opsonize fungal cells in a J774 macrophage phagocytosis and killing assay. However, only the IgG2b conferred substantial protection against mucosal and systemic candidiasis in passive vaccination experiments in rodents. Competition ELISA and microarray analyses using sequence-defined glucan oligosaccharides showed that the protective IgG2b selectively bound to β1,3-linked (laminarin-like) glucose sequences whereas the non-protective IgM bound to β1,6- and β1,4-linked glucose sequences in addition to β1,3-linked ones. Only the protective IgG2b recognized heterogeneous, polydisperse high molecular weight cell wall and secretory components of the fungus, two of which were identified as the GPI-anchored cell wall proteins Als3 and Hyr1. In addition, only the IgG2b inhibited in vitro two critical virulence attributes of the fungus, hyphal growth and adherence to human epithelial cells. Our study demonstrates that the isotype of anti-β-glucan antibodies may affect details of the β-glucan epitopes recognized, and this may be associated with a differing ability to inhibit virulence attributes of the fungus and confer protection in vivo. Our data also suggest that the anti-virulence properties
Palma AS, Liu Y, Campanero-Rhodes MA, et al., 2008, Malectin-a Novel Lectin of the Endoplasmic Reticulum and a Candidate New Player in the Early Steps Of Protein N-Glycosylation, Annual Meeting of the Society-for-Glycobiology, Publisher: OXFORD UNIV PRESS INC, Pages: 948-949, ISSN: 0959-6658
Schallus T, Jaeckh C, Feher K, et al., 2008, Malectin: a novel carbohydrate-binding protein of the endoplasmic reticulum and a candidate player in the early steps of protein N-glycosylation, Mol.Biol.Cell, Vol: 19, Pages: 3404-3414
N-Glycosylation starts in the endoplasmic reticulum (ER) where a 14-sugar glycan composed of three glucoses, nine mannoses, and two N-acetylglucosamines (Glc(3)Man(9)GlcNAc(2)) is transferred to nascent proteins. The glucoses are sequentially trimmed by ER-resident glucosidases. The Glc(3)Man(9)GlcNAc(2) moiety is the substrate for oligosaccharyltransferase; the Glc(1)Man(9)GlcNAc(2) and Man(9)GlcNAc(2) intermediates are signals for glycoprotein folding and quality control in the calnexin/calreticulin cycle. Here, we report a novel membrane-anchored ER protein that is highly conserved in animals and that recognizes the Glc(2)-N-glycan. Structure determination by nuclear magnetic resonance showed that its luminal part is a carbohydrate binding domain that recognizes glucose oligomers. Carbohydrate microarray analyses revealed a uniquely selective binding to a Glc(2)-N-glycan probe. The localization, structure, and binding specificity of this protein, which we have named malectin, open the way to studies of its role in the genesis, processing and secretion of N-glycosylated proteins
Campanero-Rhodes MA, Smith A, Chai W, et al., 2007, <i>N</i>-glycolyl GM1 ganglioside as a receptor for simian virus 40, JOURNAL OF VIROLOGY, Vol: 81, Pages: 12846-12858, ISSN: 0022-538X
- Author Web Link
- Cite
- Citations: 131
This data is extracted from the Web of Science and reproduced under a licence from Thomson Reuters. You may not copy or re-distribute this data in whole or in part without the written consent of the Science business of Thomson Reuters.