Genes for glycosylphosphatidylinositol toxin biosynthesis in Plasmodium falciparum.

Abstract	About 2.5 million people die of Plasmodium falciparum malaria every year. Fatalities are associated with systemic and organ-specific inflammation initiated by a parasite toxin. Recent studies show that glycosylphosphatidylinositol (GPI) functions as the dominant parasite toxin in the context of infection. GPIs also serve as membrane anchors for several of the most important surface antigens of parasite invasive stages. GPI anchoring is a complex posttranslational modification produced through the coordinated action of a multicomponent biosynthetic pathway. Here we present eight new genes of P. falciparum selected for encoding homologs of proteins essential for GPI synthesis: PIG-A, PIG-B, PIG-M, PIG-O, GPI1, GPI8, GAA-1, and DPM1. We describe the experimentally verified mRNA and predicted amino acid sequences and in situ localization of the gene products to the parasite endoplasmic reticulum. Moreover, we show preliminary evidence for the PIG-L and PIG-C genes. The biosynthetic pathway of the malaria parasite GPI offers potential targets for drug development and may be useful for studying parasite cell biology and the molecular basis for the pathophysiology of parasitic diseases.
Authors	Mauro Delorenzi, Adrienne Sexton, Hosam Shams-Eldin, Ralph T Schwarz, Terry Speed, Louis Schofield
Journal	Infection and immunity (Infect Immun) Vol. 70 Issue 8 Pg. 4510-22 (Aug 2002) ISSN: 0019-9567 [Print] United States
PMID	12117963 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References	Cell Adhesion Molecules DNA, Protozoan GPAA1 protein, human GPI1 protein, Plasmodium falciparum Glycosylphosphatidylinositols Gpaa1 protein, mouse Membrane Glycoproteins Membrane Proteins PIG-O protein, Plasmodium falciparum PIGK protein, human PIGO protein, human Phosphatidylinositols Protozoan Proteins Saccharomyces cerevisiae Proteins phosphatidylinositol glycan-class A protein Uridine Diphosphate N-Acetylglucosamine KRE2 protein, S cerevisiae Mannosyltransferases alpha 1-4-mannosyltransferase dolichyl-phosphate beta-D-mannosyltransferase Acetylglucosamine
Topics	Acetylation Acetylglucosamine (metabolism) Amino Acid Sequence Animals Base Sequence Cell Adhesion Molecules (genetics) DNA, Protozoan Genes, Protozoan Glycosylphosphatidylinositols (biosynthesis) Humans Mannosyltransferases (genetics) Membrane Glycoproteins (genetics) Membrane Proteins (genetics) Molecular Sequence Data Phosphatidylinositols (metabolism) Plasmodium falciparum (genetics) Protozoan Proteins (genetics) Saccharomyces cerevisiae Proteins Sequence Homology, Amino Acid Uridine Diphosphate N-Acetylglucosamine (metabolism)

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