Plasmodium falciparum AARP1, a giant protein containing repeated motifs rich in asparagine and aspartate residues, is associated with the infected erythrocyte membrane

Abstract

During Plasmodium falciparum asexual intraerythrocytic development, the host's cell plasma membrane is modified by the insertion of parasite proteins. One or more of these modifications mediate the cytoadherence of infected erythrocytes to host vascular endothelium. However, these surface antigens can be the target of cytophilic antibodies which promote phagocytosis of the infected erythrocyte. It has been proposed that antibodies directed to epitopes rich in asparagine play an important role in this process, which has promoted efforts to isolate the corresponding gene(s). We describe here P. falciparum asparagine- and aspartate-rich protein 1 (PfAARP1), a new giant (circa 700-kDa) protein associated with the infected erythrocyte membrane which is rich in asparagine and aspartate residues due to the presence of nine blocks of repeats. Topology analysis predicts that PfAARP1 has multiple transmembrane domains and at least five external loops. Human antibodies immunopurified against a sequence composed exclusively of asparagine and aspartate amino acids derived from PfAARP1 label the surface of the infected erythrocyte, demonstrating that such motifs are exposed. Interestingly, external loop 4 of PfAARP1 contains repetitions of these residues, and their possible role as a target of cytophilic antibodies is discussed.

The structural and functional diversity of Hsp70 proteins from Plasmodium falciparum

“…4) shows that some of the proteins associated with PfHsp70‐3 are a malaria antigen (MAL13P.304) and two asparagine‐rich antigen proteins (PF08_0060 and PF11_0111). This suggests a possible role of PfHsp70‐3 during protein trafficking into the erythrocyte since both malaria antigen and asparagine‐rich proteins are exported into the erythrocyte (Weber et al 1988; Barale et al 1997). Perhaps the fact that PfHsp70‐3 has been detected in the Maurer's clefts (Vincensini et al 2005; Lanzer et al 2006) suggests that this chaperone might facilitate the export of proteins of parasitic origin into the erythrocyte.…”

The malaria-infected red blood cell: Structural and functional changes

“…P. falciparum asparagine-and aspartate-rich protein 1 (PfAARP1) is still incompletely characterized but apparently it is a large protein of more than 700 kDa encoded by an approximately 20 kb gene found on chromosome 12 (Barale et al, 1997b). Structural features of this protein include nine repeat blocks rich in asparagine and aspartate residues and a PEST domain* that is found in rapidly degraded proteins.…”

“…Antisera to the PfAARPI protein reacted with the periphery of the infected red blood cell. Antibodies affinity-purified on a repeat peptide NNDDD reacted with the surface of unfixed cells (Barale et al, 1997b). Although such a result may suggest that PfAARP1 is exposed on the surface, the use of antibodies to repeat regions is fraught with technical difficulties and the possibility of artefact.…”