Metabolic labeling and structural analysis of glycosylphosphatidylinositols from parasitic protozoa.
Glycosylphosphatidylinositol (GPI) is a complex glycolipid structure that acts as a membrane anchor for many cell-surface proteins of eukaryotes. GPI-anchored proteins are particularly abundant in protozoa and represent the major carbohydrate modification of many cell-surface parasite proteins. A minimal GPI-anchor precursor consists of core glycan (ethanolamine-P-Manalpha1-2Manalpha1-6Manalpha1-4GlcNH2) linked to the 6-position of the D-myo-inositol ring of phos-phatidylinositol. Although the GPI core glycan is conserved in all organisms, many differences in additional modifications to GPI structures and biosynthetic pathways have been reported. The preassembled GPI-anchor precursor is post-translationally transferred to a variety of membrane proteins in the lumen of the endoplasmic reticulum in a transamidase-like reaction during which a C-terminal GPI attachment signal is released. Increasing evidence show that a significant proportion of the synthesized GPIs are not used for protein anchoring, particularly in protozoa in which a large amount of free GPIs are being displayed at the cell surface. The characteristics of GPI biosynthesis are currently being explored for the development of parasite-specific inhibitors. Especially as this pathway, at least for Trypanosoma brucei, has been validated as a drug target.
Azzouz
Nahid
N
Laboratory for Organic Chemistry, Swiss Federal Institute of Technology, Zürich, Switzerland.
Gerold
Peter
P
Schwarz
Ralph T
RT
D000818:Animals; D002236:Carbohydrate Conformation; D002851:Chromatography, High Pressure Liquid; D002852:Chromatography, Ion Exchange; D017261:Glycosylphosphatidylinositols / Q000737:chemistry / Q000378:metabolism*; D010963:Plasmodium falciparum / Q000378:metabolism*
D017261:Glycosylphosphatidylinositols