The GPI1 homologue from Plasmodium falciparum complements a Saccharomyces cerevisiae GPI1 anchoring mutant.

Glycosylphosphatidylinositol (GPI) represents an important anchoring molecule for cell surface proteins. The first step in its synthesis is the transfer of N-acetylglucosamine (GlcNAc) from UDP-N-acetylglucosamine to phosphatidylinositol (PI). This chemically simple step is genetically complex because three or four genes are required in both yeast (GPI1, GPI2 and GPI3) and mammals (GPI1, PIG A, PIG H and PIG C), respectively. Here, we report cloning of a Plasmodium falciparum (P. falciparum) homologue of GPI1 (PfGPI1). Analysis showed that P. falciparum Gpi1p is somewhat more similar to the yeast proteins than human Gpi1p, showing 26 and 20% amino acid sequence identity with the Saccharomyces cerevisiae and Homo sapiens proteins, respectively. Multiple sequence alignment demonstrates also that the C-terminal half GPI1 proteins is much better conserved than the N-terminal half. The P. falciparum Gpi1p has a calculated molecular weight of 65 kDa and a predicted potential tyrosine phosphorylation site. The potential tyrosine phosphorylation site seems to occur in all other known Gpi1 proteins. Like the other GPI1 proteins, the predictive software revealed the absence of targeting signals such as organelle transit peptides, DNA binding sites, or N-terminal secretory signals. Hydrophobicity plots revealed multiple hydrophobic regions that could function as transmembrane segments. The cloned P. falciparum GPI1 gene complemented a gpi1 yeast mutant.