Function and mechanism of o-fucosylation of malaria parasite tsr-domain proteins

Thrombospondin type-1 repeat (TSR) domains play essential roles in gliding motility, host-cell recognition and invasion throughout the life cycle of the malaria parasite, Plasmodium falciparum. These domains are present in proteins that are particularly important during parasite transmission from humans to mosquitoes and back. As it has been described across diverse organisms, TSR domains are commonly fucosylated by the protein-O-fucosyltransferase 2 (PoFUT2) and this modification is required for optimal folding and secretion of TSR-containing proteins. Furthermore, the o-fucosylation consensus sequence on TSR domains coincides with its ligand-binding motif, suggesting that O-fucose may alter ligand-binding affinities of TSR-domains. A PoFUT2 homolog is conserved and expressed by P. falciparum, and GDP-fucose, the substrate donor of o-fucosylation reactions, is actively synthesized and incorporated by the parasite. Together with the detection of the o-fucosylation machinery in salivary gland sporozoites by proteomic analyses, the evidence strongly points to the conservation of a PoFUT2 mediated o-fucosylation mechanism in P. falciparum.

TSR domains are essential for host- parasite interactions in malaria. A deeper insight into a mechanism of posttranslational modification of P. falciparum TSR will ultimately lay the foundation for future exploration into the fundamental role of glycosylation in malaria parasite biology

NIH RePORTFunction and mechanism of O-fucosylation of malaria TSR-domain proteins

Genetics and Genomics

Dec 2014 — Nov 2016

$383,593

United States