Phenylmethanesulphonyl fluoride inhibits GPI anchor biosynthesis in the African trypanosome

Wayne J. Masterson, Michael A. J. Ferguson

    Research output: Contribution to journalArticle

    31 Citations (Scopus)

    Abstract

    A wide variety of eukaryotic membrane proteins are anchored to the outside of cells by covalent linkage to glycosyl phosphatidylinositol (GPI). One of the best characterized examples is the variant surface glycoprotein (VSG) of the protozoan parasite, Trypanosoma brucei. The structure of the GPI precursor is ethanolamine-PO4-Mana1-2Mana1-6Mana1-4GlcNH2-PI; the phosphoethanolamine moiety forms an amide linkage to the VSG polypeptide a-COOH group during its attachment to protein. Here we report that the serine esterase inhibitor, phenylmethanesulphonyl fluoride (PMSF), inhibits phosphoethanolamine incorporation into the GPI precursor resulting in the accumulation of a Man3GlcNH2-PI intermediate. PMSF exerts this effect both in living trypanosomes and in a trypanosome-derived cell-free system. This is the first report of an inhibitor which affects GPI biosynthesis but not N-glycosylation. A model of the mechanism of phosphoethanolamine incorporation into the GPI precursor, based on the known properties of PMSP, is presented.

    Original languageEnglish
    Pages (from-to)2041-2045
    Number of pages5
    JournalEMBO Journal
    Volume10
    Issue number8
    Publication statusPublished - Aug 1991

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