Biosynthesis ofO -N -Acetylglucosamine-linked Glycans inTrypanosoma cruzi

Previato, José O.; Sola‐Penna, Mauro; Agrellos, Orlando A.; Jones, Christopher; Oeltmann, Thomas N.; Travassos, Luiz R.

doi:10.1074/jbc.273.24.14982

Cited by 71 publications

(43 citation statements)

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“…7D). Analysis of a peptide from a T. cruzi mucin, containing authentic GlcNAc␣1-Thr (6), yielded peaks at the positions of G and S, and these also were present at ratio of 1.36 (Fig. 7B).…”

Section: Figmentioning

confidence: 99%

“…For the GlcNAc␣1-Thr standard, a GlcNAc-rich peptide preparation was derived from a sialoglycoprotein fraction from T. cruzi by periodate oxidation and partial acid hydrolysis, as described (6). This fraction contained almost exclusively GlcNAc␣1-Thr as determined by NMR, and was provided by J. Previato (Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil).…”

Section: Edman Degradationmentioning

confidence: 99%

“…In Trypanosoma cruzi, addition of ␣-GlcNAc to Thr residues of glycosylphosphatidylinositol-anchored cell surface mucins has been reconstituted in vitro using a Golgi extract (6,12), but thus far the gene and protein responsible for this activity have not been identified. Evidence suggests that mucin O-glycosylation is a critical virulence factor for this organism in causing Chagas disease (13).…”

mentioning

confidence: 99%

“…Extracellular mucin proteins are employed throughout the eukaryotic kingdom as physical and chemical protective barriers with signaling functions at the cell surface (1)(2)(3)(4)(5)(6). Mucintype domains in these proteins are characterized by multiple repeats of short polypeptide sequences rich in the amino acids Thr, Ser, Pro, Hyp (hydroxyproline), Gly, and/or Val, and the hydroxyamino acids are subject to extensive O-glycosylation.…”

mentioning

confidence: 99%

“…The GalNAc is normally extended by Gal and/or other sugars, which are capped by anionic substituents such as sialic acid or SO 4 . The O-glycans impose conformational rigidity to the polypeptide (10), protect it from proteolysis (11), and may constitute ligands for receptors or decoys for parasites (1)(2)(3)(4)(5)(6). Mucin proteins also typically have Nand/or C-terminal Cys-rich domains, the Cys residues of which participate in intra-and intermolecular disulfide bonds that cross-bridge the proteins into extensive networks (2,5).…”

mentioning

confidence: 99%

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Initiation of Mucin-type O-Glycosylation in Dictyostelium Is Homologous to the Corresponding Step in Animals and Is Important for Spore Coat Function

Wang

Metcalf

Wel

et al. 2003

Journal of Biological Chemistry

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Like animal cells, many unicellular eukaryotes modify mucin-like domains of secretory proteins with multiple O-linked glycans. Unlike animal mucin-type glycans, those of some microbial eukaryotes are initiated by ␣-linked GlcNAc rather than ␣-GalNAc. Based on sequence similarity to a recently cloned soluble polypeptide hydroxyproline GlcNAc-transferase that modifies Skp1 in the cytoplasm of the social ameba Dictyostelium, we have identified an enzyme, polypeptide ␣-N-acetylglucosaminyltransferase (pp ␣-GlcNAc-T2), that attaches GlcNAc to numerous secretory proteins in this organism. Unlike the Skp1 GlcNAc-transferase, pp ␣-GlcNAc-T2 is predicted to be a type 2 transmembrane protein. A highly purified, soluble, recombinant fragment of pp ␣-GlcNAc-T2 efficiently transfers GlcNAc from UDP-GlcNAc to synthetic peptides corresponding to mucin-like domains in two proteins that traverse the secretory pathway. pp ␣-GlcNAc-T2 is required for addition of GlcNAc to peptides in cell extracts and to the proteins in vivo. Mass spectrometry and Edman degradation analyses show that pp ␣-GlcNAc-T2 attaches GlcNAc in ␣-linkage to the Thr residues of all the synthetic mucin repeats. pp ␣-GlcNAc-T2 is encoded by the previously described modB locus defined by chemical mutagenesis, based on sequence analysis and complementation studies. This finding establishes that the many phenotypes of modB mutants, including a permeability defect in the spore coat, can now be ascribed to defects in mucin-type O-glycosylation. A comparison of the sequences of pp ␣-GlcNAc-T2 and the animal pp ␣-GalNAc-transferases reveals an ancient common ancestry indicating that, despite the different N-acetylhexosamines involved, the enzymes share a common mechanism of action.

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Section: Figmentioning

confidence: 99%

Section: Edman Degradationmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%