(A) The structure of GPIs of the blood-stage Plasmodium falciparum as determined by biochemical analyses and mass spectrometry. GPI anchoring of proteins via an amide bond between the terminal carboxyl group of proteins and amino group of ethanolamine phosphate (EtNP) is indicated. The glycan structure, Man4-GlcN-myo-insoitol, is conserved
across various P. falciparum isolates and rodent malaria parasite species. The fatty acid substitution of P. falciparum GPIs is highly heterogeneous and is dependent on host blood fatty acid composition during infection, as parasites predominantly use fatty acids of host blood for the synthesis of various membrane lipids. The fatty acid composition of GPIs of P. falciparum grown in pooled human sera is indicated. Note: The sn-1 and sn-2 positions are invariably substituted with saturated and unsaturated fatty acids, respectively, and inositol is substituted with shorter saturated fatty acids. (B) The upper panel shows the two matured GPIs containing EtNP substitution and the GPI biosynthetic intermediates of P. falciparum that have been biochemically identified. The lower panel shows the parasite GPI biosynthetic pathway. (C–F) Glycosylation features of parasites: N-glycosylation (C); O-GlcNAcylation (D); O-fucosylation of the ThromboSpondin Repeat (TSR) domains (E); C-mannosylation of TSR domains (F). (E) The TSR domains are mainly modified with single residues of Fuc, and in some TSR domains, Fuc is substituted with a terminal Glc (not shown). Abbreviations: ALG7, asparagine-linked glycosylation gene 7; Dol-P, dolichol phosphate; Fuc, fucose; Glc, glucose; GlcN, glucosamine; GlcNAc, N-acetylglucosamine; Ino, inositol; Man, mannose; ManT, mannosyltransferase; OGA, O-GlcNAcase; OGT, O-N-acetylglucosaminyltransferase; OST, oligosaccharyltransferase; PE. phosphatidylethanolamine; PI, phosphatidylinositol; PIGA, phosphatidylinositol glycan gene A; POFUT2; protein O-fucosyl-transferase 2.
Gowda DC, Miller LH. Glycosylation in malaria parasites: what do we know? Trends Parasitol. 2024 22:S1471-4922(23)00311-2. PMID: 38262838.