A novel Plasmodium falciparum erythrocyte binding protein-2 (EBP2/BAEBL) involved in erythrocyte receptor binding.
The 175-kDa erythrocyte binding protein (EBA-175) of Plasmodium falciparum and Duffy antigen binding proteins of P. vivax and P. knowlesi are members of a protein family. The features of this protein family include a cysteine-rich motif present in the erythrocyte receptor-binding domain. We identify here a novel 140-kDa P. falciparum erythrocyte binding protein (EBP2/BAEBL) containing the signature cysteine-rich motif by comparative analysis of gene sequence information. Polyclonal antibodies generated by immunization with an EBP2/BAEBL DNA vaccine immunoprecipitated a 140-kDa protein from P. falciparum schizont-infected erythrocyte lysates. Similar to EBA-175, the binding of EBP2/BAEBL to human erythrocytes was dependent on sialic acids because neuraminidase treatment of those erythrocytes rendered them incapable of binding, but differed from EBA-175 in that trypsin treatment decreased EBP2/BAEBL binding by only twofold compared to a 10-fold reduction in EBA-175 binding. Antibodies raised against the putative erythrocyte-binding domain of EBP2/BAEBL effectively blocked the binding of native EBP2/BAEBL to erythrocytes. These functional antibodies localize EBP2/BAEBL to the invasive apical end of the merozoite. We identify EBP2/BAEBL as a paralogue of EBA-175 and as a novel P. falciparum vaccine candidate.
Narum
David L
DL
EntreMed, Inc., 9640 Medical Center Drive, Rockville, MD 20850, USA.
Fuhrmann
Steven R
SR
Luu
Tin
T
Sim
B Kim Lee
BK
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D000953:Antigens, Protozoan; D015153:Blotting, Western; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics* / Q000276:immunology / Q000378:metabolism*; D003545:Cysteine / Q000235:genetics / Q000378:metabolism; D023061:Gene Order; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008565:Membrane Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010963:Plasmodium falciparum / Q000235:genetics*; D011485:Protein Binding; D015800:Protozoan Proteins / Q000737:chemistry / Q000235:genetics* / Q000276:immunology / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000235:genetics* / Q000276:immunology / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D063267:Sialic Acid Binding Ig-like Lectin 1
D000953:Antigens, Protozoan; D002352:Carrier Proteins; C066001:Duffy antigen binding protein, Plasmodium; D007074:Immunoglobulin G; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D015800:Protozoan Proteins; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; C571166:SIGLEC1 protein, human; D063267:Sialic Acid Binding Ig-like Lectin 1; C571167:Siglec1 protein, mouse; C451423:erythrocyte binding protein-2, Plasmodium falciparum; C065668:erythrocyte-binding antigen 175, Plasmodium; D003545:Cysteine