The domain on the mouse Duffy protein for Plasmodium yoelii binding and invasion to mouse erythrocytes.
Erythrocyte invasion by malaria parasites is a multi-step process requiring specific molecular interactions between merozoites and erythrocyte surface receptors. Human Duffy blood group protein is the receptor for Plasmodium vivax merozoite invasion to red blood cells. The cognate parasite ligand for Duffy protein is a 135 kDa Duffy binding protein (DBP). Previously, we defined the domain on the N-terminus of human Duffy protein required for DBP binding and showed that a 35-mer N-terminal peptide inhibited DBP binding to Duffy positive red cells in vitro. There is no efficient in vitro culture system or small animal model to study P. vivax ligand binding and invasion to red blood cells. Plasmodium yoelii is frequently used to study the interaction between host receptors and parasite ligands. Similar to human parasite P. vivax, rodent malaria parasite P. yoelii also uses Duffy protein on mouse RBCs for invasion. However, the domain on the mouse Duffy for P. yoelii binding is not known. In this communication, using a mouse model, we show that an antibody against the N-terminus of mouse Duffy protein inhibited P. yoelii invasion in the mouse. In addition, by using small peptides from the N-terminal exocellular domain, we defined the domain on the Duffy protein for P. yoelii binding and invasion to mouse erythrocytes. Our results also indicated that small peptides from the host receptor could act as decoy receptors and may be utilized as potential antimalarial drugs.
Xu
Lili
L
Laboratory of Cell Biology, New York Blood Center, NY 10021, USA.
Niu
Jinkui
J
Chaudhuri
Asok
A
D000818:Animals; D008297:Male; D051379:Mice; D000911:Antibodies, Monoclonal; D000953:Antigens, Protozoan / Q000276:immunology / Q000378:metabolism; D000962:Antimalarials / Q000378:metabolism / Q000494:pharmacology; D004195:Disease Models, Animal; D004375:Duffy Blood-Group System / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D004912:Erythrocytes / Q000469:parasitology; D008288:Malaria / Q000469:parasitology; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018512:Parasitemia; D010455:Peptides / Q000378:metabolism / Q000494:pharmacology; D010967:Plasmodium yoelii / Q000472:pathogenicity; D017434:Protein Structure, Tertiary; D015800:Protozoan Proteins / Q000276:immunology / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000276:immunology / Q000378:metabolism
C473745:ACKR1 protein, human; D000911:Antibodies, Monoclonal; D000953:Antigens, Protozoan; D000962:Antimalarials; C066001:Duffy antigen binding protein, Plasmodium; D004375:Duffy Blood-Group System; D010455:Peptides; D015800:Protozoan Proteins; D011956:Receptors, Cell Surface; C483025:Ackr1 protein mouse