PfRH5: a novel reticulocyte-binding family homolog of plasmodium falciparum that binds to the erythrocyte, and an investigation of its receptor.
Multiple interactions between parasite ligands and their receptors on the human erythrocyte are a condition of successful Plasmodium falciparum invasion. The identification and characterization of these receptors presents a major challenge in the effort to understand the mechanism of invasion and to develop the means to prevent it. We describe here a novel member of the reticulocyte-binding family homolog (RH) of P. falciparum, PfRH5, and show that it binds to a previously unrecognized receptor on the RBC. PfRH5 is expressed as a 63 kDa protein and localized at the apical end of the invasive merozoite. We have expressed a fragment of PfRH5 which contains the RBC-binding domain and exhibits the same pattern of interactions with the RBC as the parent protein. Attachment is inhibited if the target cells are exposed to high concentrations of trypsin, but not to lower concentrations or to chymotrypsin or neuraminidase. We have determined the affinity, copy number and apparent molecular mass of the receptor protein. Thus, we have shown that PfRH5 is a novel erythrocyte-binding ligand and the identification and partial characterization of the new RBC receptor may indicate the existence of an unrecognized P. falciparum invasion pathway.
Rodriguez
Marilis
M
Laboratory of Blood-Borne Parasites, Lindsley Kimball Research Institute, The New York Blood Center, New York, New York, USA.
Lustigman
Sara
S
Montero
Estrella
E
Oksov
Yelena
Y
Lobo
Cheryl A
CA
D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D002918:Chymotrypsin / Q000494:pharmacology; D004910:Erythrocyte Membrane / Q000378:metabolism*; D006801:Humans; D009439:Neuraminidase / Q000494:pharmacology; D010963:Plasmodium falciparum / Q000254:growth & development / Q000378:metabolism*; D011485:Protein Binding; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000378:metabolism; D014357:Trypsin / Q000494:pharmacology
D002352:Carrier Proteins; C531020:RH5 protein, Plasmodium falciparum; D011956:Receptors, Cell Surface; D009439:Neuraminidase; D002918:Chymotrypsin; D014357:Trypsin