Malaria, transmitted by the parasite Plasmodium falciparum, is a devastating disease causing more than one million deaths each year targeting severely new-borns and children. Malaria during pregnancy is one of the most severe forms. Infected red blood cells in placenta express a specific protein called VAR2CSA involved in the adhesion and invasion of the placenta. VAR2CSA, a large protein of 350 kDa, is characterized by six DBL domains tbat interact witb the host cell receptor chondroitin sulpbate A (CSA), a glucosaminoglycan (GAG) polysaccharide largely present in placenta. Three DBL domains DBL2x, DBL3x and DBL6e of VAR2CSA have been shown to interact with CSA. The crystallographic structures of DBL3x and DBL6e reveal a helical core surrounded by flexible loops not clearly observable by crystallography. Also, due to high heterogeneity of the CSA polysaccharide, the CSA binding site for both DBL domains has not yet been described. Therefore, we propose to elucidate the mechanism of CSA recognition by DBL3x and DBL6e domains combining NMR and crystallography with biophysical studies. Finally, the use of nanobodies against DBLs will be advantageous to correlate our structural model of the DBLlCSA interaction with the adhesion of Plasmodium to placenta in vivo.
|Effective start/end date||1/10/10 → 30/09/14|
Flemish discipline codes
- Biological sciences
- Applied Biology