Glycosylphosphatidylinositol biosynthesis validated as a drug target for African sleeping sickness

Glycosylphosphatidylinositol (GPI) membrane-anchored proteins have attracted considerable attention as markers of detergent-insoluble cholesterol/sphingolipid-rich “lipid rafts” (1). GPI-anchored proteins are ubiquitous among the eukaryotes and are particularly abundant, in terms of surface density, in a number of protozoan organisms. The term GPI was first introduced in 1985 for the membrane anchor of the variant surface glycoprotein (VSG) of Trypanosoma brucei and the first complete GPI structure (2) and descriptions of GPI biosynthesis (3, 4) were for T. brucei VSG.