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Mass Spectrometric Identification of Aberrantly Glycosylated Human Apolipoprotein C-III Peptides in Urine from Schistosoma mansoni-infected Individuals*

https://doi.org/10.1074/mcp.M900537-MCP200Get rights and content
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Schistosomiasis is a parasitic infection caused by Schistosoma flatworms, prime examples of multicellular parasites that live in the mammalian host for many years. Glycoconjugates derived from the parasite have been shown to play an important role in many aspects of schistosomiasis, and some of them are present in the circulation of the host. The aim of this study was to identify novel glycoconjugates related to schistosomiasis in urine of Schistosoma mansoni-infected individuals using a combination of glycopeptide separation techniques and in-depth mass spectrometric analysis. Surprisingly, we characterized a heterogeneous population of novel aberrantly O-glycosylated peptides derived from the C terminus of human apolipoprotein C-III (apoC-III) in urine of S. mansoni-infected individuals that were not detected in urine of non-infected controls. The glycan composition of these glycopeptides is completely different from what has been described previously for apoC-III. Most importantly, they lack sialylation and display a high degree of fucosylation. This study exemplifies the potential of mass spectrometry for the identification and characterization of O-glycopeptides without prior knowledge of either the glycan or the peptide sequence. Furthermore, our results indicate for the first time that as a result of S. mansoni infection the glycosylation of a host protein is altered.

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*

This work was supported by the European Union Sixth Framework Program (Multi-Disciplinary Studies of Human Schistosomiasis in Uganda, Kenya and Mali: New Perspectives on Morbidity, Immunity, Treatment and Control (MUSTSchistUKEMA), Contract 517733).

This article contains a supplemental ion trap CID MS/MS spectrum of aberrantly glycosylated apoC-III peptide WDLDPEVRPTSA carrying H2N2F2 (m/z 1204.2, [M + 2H]2+).

1

The abbreviations used are:

    CCA

    circulating cathodic antigen

    apo

    apolipoprotein

    SCX

    strong cation exchange chromatography

    HILIC

    hydrophilic interaction liquid chromatography

    MQ

    Milli-Q

    RT

    room temperature

    Hex or H

    hexose

    HexNAc or N

    N-acetylhexosamine

    Fuc or F

    fucose

    epg

    eggs/g of feces

    BLAST

    Basic Local Alignment Search Tool.