Unique Asn-linked oligosaccharides of the human pathogen Entamoeba histolytica

Department of Molecular and Cell Biology, Department of Biochemistry, Boston University Medical Center, Boston, MA 02118-2526, USA.
Journal of Biological Chemistry (Impact Factor: 4.57). 07/2008; 283(26):18355-64. DOI: 10.1074/jbc.M800725200
Source: PubMed


N-Glycans of Entamoeba histolytica, the protist that causes amebic dysentery and liver abscess, are of great interest for multiple reasons. E. histolytica makes an unusual truncated N-glycan precursor (Man5GlcNAc2), has few nucleotide sugar transporters, and has a surface that is capped by the lectin concanavalin A. Here, biochemical
and mass spectrometric methods were used to examine N-glycan biosynthesis and the final N-glycans of E. histolytica with the following conclusions. Unprocessed Man5GlcNAc2, which is the most abundant E. histolytica N-glycan, is aggregated into caps on the surface of E. histolytica by the N-glycan-specific, anti-retroviral lectin cyanovirin-N. Glc1Man5GlcNAc2, which is made by a UDP-Glc: glycoprotein glucosyltransferase that is part of a conserved N-glycan-dependent endoplasmic reticulum quality control system for protein folding, is also present in mature N-glycans. A swainsonine-sensitive α-mannosidase trims some N-glycans to biantennary Man3GlcNAc2. Complex N-glycans of E. histolytica are made by the addition of α1,2-linked Gal to both arms of small oligomannose glycans, and Gal residues are capped by one
or more Glc. In summary, E. histolytica N-glycans include unprocessed Man5GlcNAc2, which is a target for cyanovirin-N, as well as unique, complex N-glycans containing Gal and Glc.

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    • "incorporation of deoxyhexoses nor additional GlcNAc residues could be detected (Magnelli, et al. 2008). Similarly in several strains of Trichomonas vaginalis, a widespread sexuallytransmitted parasite, the major glycan detectable is also Man 5 GlcNAc 2 (see Figure 2); however, much additional variation was also observed. "
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    ABSTRACT: Although countless genomes have now been sequenced, the glycomes of the vast majority of eukaryotes still present a series of unmapped frontiers. However, strides are being made in a few groups of invertebrate and unicellular organisms as regards their N-glycans and N-glycosylation pathways. Thereby, the traditional classification of glycan structures inevitably approaches its boundaries. Indeed, the glycomes of these organisms are rich in surprises, including a multitude of modifications of the core regions of N-glycans and unusual antennae. From the actually rather limited glycomic information we have, it is nevertheless obvious that the biotechnological, developmental and immunological relevance of these modifications, especially in insect cell lines, model organisms and parasites means that deciphering unusual glycomes is of more than just academic interest.
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    • "That only GNL, which exclusively binds to terminal α(1– 3)-linked mannose residues in N-linked glycans [29] [39], which inhibited the adherence and cytotoxicity of E. histolytica, suggests that the amoebic lectin contains N-glycans with terminal α(1–3)- linked mannose residues near to the carbohydrate recognition domain. A recent study reported that N-glycans of amoeba contain terminal α(1–3)-linked mannose residues [40]. Furthermore, Nlinked glycans in the heavy chain of the galactose-specific lectin play a key role in the adherence of E. histolytica to host cells [41]. "
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    ABSTRACT: The human large intestine can harbor two morphologically similar amoebae; the invasive Entamoeba histolytica and the non-invasive Entamoeba dispar. Whereas E. histolytica can produce intestinal and extra-intestinal lesions, E. dispar is present in non-symptomatic carriers. Although biochemical, genetic and proteomic studies have identified clear differences between these Entamoebae, it has become clear that several molecules, once assumed to be involved in tissue destruction, exist in both the virulent and the avirulent species. As surface molecules may play a role in invasion and could therefore determine which amoebae are invasive, we analyzed the glycoconjugate composition of E. histolytica and E. dispar using lectins. There was a significant difference between E. histolytica and E. dispar in the expression of glycoconjugates containing d-mannose and N-acetyl-alpha-D-galactosamine residues, but not between virulent and avirulent strains of E. histolytica. N-glycoconjugates with terminal alpha (1-3)-linked mannose residues participate in the adhesion and subsequent cytotoxicity of E. histolytica to cultured hamster hepatocytes. One of them probably is the Gal/GalNAc lectin.
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    ABSTRACT: Glycoprotein structures are remarkably simple in Giardia. This protist produces the shortest Asn-linked glycan (N-glycan) yet described: two N-acetyl-glucosamines (GlcNAc2). The oligosaccharyltransferase (OST) that transfers N-glycans to the peptide has a single catalytic subunit in Giardia but contains four to eight subunits in most eukaryotes. Giardia is missing the ER proteins involved in N-glycan-dependent quality conrol (QC) of protein folding and degradation. There is Darwinian selection for the sites of N-glycan in secreted proteins of eukaryotes with N-glycan-dependent QC, but there is no such selection in Giardia and other protists lacking N-glycan-dependent QC. The glycosylphosphatidylinositol (GPI) anchor of Giardia is predicted to be the simplest of any eukaryote. UDP-GlcNAc is the only nucleotide sugar transported from the cytosol to the lumen of the ER. By contrast, Giardia is one of the rare protists that use GlcNAc to modify Ser and Thr residues on nucleocytosolic proteins. WGA affinity dramatically enriches glycoproteins of Giardia, many of which are unique or are encystation specific. In summary, GlcNAc is the major sugar added to Giardia glycoproteins, which are much less complex than those of the host.
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