Structural studies of N-glycans of filarial parasites. Conservation of phosphorylcholine-substituted glycans among species and discovery of novel chito-oligomers

N-Type glycans containing phosphorylcholine (PC-glycans), unusual structures found in the important human pathogens filarial nematodes, represent a novel target for chemotherapy. Previous work in our laboratories produced compositional information on the PC-glycan of ES-62, a secreted protein of the...

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Bibliographic Details
Published in:The Journal of biological chemistry 1999-07, Vol.274 (30), p.20953-20960
Main Authors: Haslam, S M, Houston, K M, Harnett, W, Reason, A J, Morris, H R, Dell, A
Format: Article
Language:English
Subjects:
Animals
Dipetalonema - chemistry
Dipetalonema - genetics
Gerbillinae - parasitology
Humans
Mass Spectrometry
Onchocerca volvulus - chemistry
Onchocerca volvulus - genetics
Phosphorylcholine - chemistry
Polysaccharides - chemistry
Polysaccharides - genetics
Species Specificity
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Summary:N-Type glycans containing phosphorylcholine (PC-glycans), unusual structures found in the important human pathogens filarial nematodes, represent a novel target for chemotherapy. Previous work in our laboratories produced compositional information on the PC-glycan of ES-62, a secreted protein of the rodent parasite Acanthocheilonema viteae. In particular, we established using fast atom bombardment mass spectrometry (MS) analysis that PC was attached to a glycan with a trimannosyl core, with and without core fucosylation, carrying between one and four additional N-acetylglucosamine residues. In the present study, we demonstrate that this structure is conserved among filarial nematodes, including the parasite of humans, Onchocerca volvulus, for which new drugs are most urgently sought. Furthermore, by employing a variety of procedures, including collision-activated dissociation MS-MS analysis and matrix-assisted laser desorption MS analysis, we reveal that surprisingly, filarial nematodes also contain N-linked glycans, the antennae of which are composed of chito-oligomers. To our knowledge, this is the first report of such structures in a eukaryotic glycoprotein.
ISSN:0021-9258
DOI:10.1074/jbc.274.30.20953