A novel Plasmodium falciparum erythrocyte binding protein associated  with the merozoite surface, PfDBLMSP.
Proteins on the surface of the merozoite, the invasive form of the malaria parasite Plasmodium falciparum,and those secreted from its apical secretory organelles are promising vaccine candidates against blood stage malaria. In the present study, we have identified a novel parasite protein (PfDBLMSP; Gene IDPF10_0348), that harbors a predicted signal sequence, a central Duffy binding-like (DBL) domain and a secreted polymorphic antigen associated with merozoites (SPAM) domain in its C-terminal half. Transcription and translation of pfdblmsp is up-regulated specifically in schizont stage parasites, similar to other well-chararacterized merozoite proteins involved in invasion of red blood cells (RBCs). PfDBLMSPwas localized on the merozoite surface with a GFP targeting approach using schizont-stage specific expression systems, and by immunofluorescence assays of the endogenous protein. PfDBLMSP expressed on the surface of mammalian cells (COS-7) showed binding with human RBCs and this binding was sensitive to trypsin and neuraminidase treatments. The recombinant proteins corresponding to the DBL and SPAM domains showed reactivity with immune sera from individuals residing in P. falciparum endemic areas. Polymorphism in PfDBLMSP sequences from different P. falciparum strains and field isolates suggested that its DBL domain is under natural immune pressure. Our data on localization and functional assays suggest a possible role of PfDBLMSP in binding of merozoites with erythrocytes during invasion.
International Centre for Genetic Engineering and Biotechnology, New Delhi, India.
Thilan
T
Wickramarachchi
Ana L
AL
Cabrera
Dipto
D
Sinha
Shikha
S
Dhawan
Thyageshwar
T
Chandran
Yengkhom S
YS
Devi
Maya
M
Kono
Tobias
T
Spielmann
Tim W
TW
Gilberger
Virander S
VS
Chauhan
Asif
A
Mohmmed
D000595:Amino Acid Sequence; D000818:Animals; D000913:Antibodies, Protozoan; D015152:Blotting, Northern; D015153:Blotting, Western; D019556:COS Cells; D002352:Carrier Proteins / Q000235:genetics / Q000276:immunology; D002522:Chlorocebus aethiops; D004797:Enzyme-Linked Immunosorbent Assay; D004912:Erythrocytes / Q000276:immunology / Q000378:metabolism* / Q000469:parasitology; D006801:Humans; D016778:Malaria, Falciparum / Q000276:immunology / Q000469:parasitology / Q000517:prevention & control; D008565:Membrane Proteins; D020066:Merozoite Surface Protein 1 / Q000235:genetics*; D052940:Merozoites / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010963:Plasmodium falciparum / Q000235:genetics* / Q000276:immunology; D011485:Protein Binding / Q000235:genetics / Q000276:immunology; D021382:Protein Sorting Signals; D015800:Protozoan Proteins / Q000235:genetics* / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid
D000913:Antibodies, Protozoan; D002352:Carrier Proteins; D008565:Membrane Proteins; D020066:Merozoite Surface Protein 1; D021382:Protein Sorting Signals; D015800:Protozoan Proteins; D011993:Recombinant Fusion Proteins