Identification of glycosaminoglycan binding domains in Plasmodium falciparum erythrocyte membrane protein 1 of a chondroitin sulfate A-adherent parasite.
Accumulation of Plasmodium falciparum-infected erythrocytes in the placenta is a key feature of maternal malaria. This process is mediated in part by the parasite ligand P. falciparum erythrocyte membrane protein 1 (PfEMP1) at the surface of the infected erythrocyte interacting with the host receptor chondroitin sulfate A (CSA) on the placental lining. We have localized CSA binding activity to two adjacent domains in PfEMP1 of an adherent parasite line and shown the presence of at least three active glycosaminoglycan binding sites. A putative CSA binding sequence was identified in one domain, but nonlinear binding motifs are also likely to be present, since binding activity in the region was shown to be dependent on conformation. Characterization of this binding region provides an opportunity to investigate further its potential as a target for antiadhesion therapy.
Reeder
J C
JC
Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3050, Australia. imrgka@datec.com.pg
Hodder
A N
AN
Beeson
J G
JG
Brown
G V
GV
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites / Q000235:genetics; D002448:Cell Adhesion; D002809:Chondroitin Sulfates / Q000378:metabolism*; D004910:Erythrocyte Membrane / Q000469:parasitology; D005260:Female; D006025:Glycosaminoglycans / Q000378:metabolism*; D006801:Humans; D016778:Malaria, Falciparum / Q000097:blood / Q000150:complications / Q000469:parasitology; D008969:Molecular Sequence Data; D010920:Placenta / Q000469:parasitology; D010963:Plasmodium falciparum / Q000235:genetics / Q000378:metabolism*; D011247:Pregnancy; D015597:Pregnancy Complications, Parasitic / Q000097:blood / Q000469:parasitology; D017434:Protein Structure, Tertiary / Q000235:genetics; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism*
D006025:Glycosaminoglycans; D015800:Protozoan Proteins; C085731:erythrocyte membrane protein 1, Plasmodium falciparum; D002809:Chondroitin Sulfates