title: A thrombospondin structural repeat containing rhoptry protein from Plasmodium falciparum mediates erythrocyte invasion.
abstract: Host cell invasion by Plasmodium falciparum requires multiple molecular interactions between host receptors and parasite ligands. A family of parasite proteins, which contain the conserved thrombospondin structural repeat motif (TSR), has been implicated in receptor binding during invasion. In this study we have characterized the functional role of a TSR containing blood stage protein referred to as P. falciparum thrombospondin related apical merozoite protein (PfTRAMP). Both native and recombinant PfTRAMP bind untreated as well as neuraminidase, trypsin or chymotrypsin-treated human erythrocytes. PfTRAMP is localized in the rhoptry bulb and is secreted during invasion. Adhesion of microneme protein EBA175 with its erythrocyte receptor glycophorin A provides the signal that triggers release of PfTRAMP from the rhoptries. Rabbit antibodies raised against PfTRAMP block erythrocyte invasion by P. falciparum suggesting that PfTRAMP plays an important functional role in invasion. Combination of antibodies against PfTRAMP with antibodies against microneme protein EBA175 provides an additive inhibitory effect against invasion. These observations suggest that targeting multiple conserved parasite ligands involved in different steps of invasion may provide an effective strategy for the development of vaccines against blood stage malaria parasites.
authors: Malaria Group, International Centre for Genetic Engineering and Biotechnology (ICGEB), New Delhi, India.
authors: Faiza Amber
authors: FA
authors: Siddiqui
authors: Shikha
authors: S
authors: Dhawan
authors: Shailja
authors: S
authors: Singh
authors: Bijender
authors: B
authors: Singh
authors: Pankaj
authors: P
authors: Gupta
authors: Alok
authors: A
authors: Pandey
authors: Asif
authors: A
authors: Mohmmed
authors: Deepak
authors: D
authors: Gaur
authors: Chetan E
authors: CE
authors: Chitnis
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D000953:Antigens, Protozoan / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D004912:Erythrocytes / Q000378:metabolism / Q000469:parasitology*; D006021:Glycophorins / Q000378:metabolism; D008565:Membrane Proteins / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D051379:Mice; D023421:Models, Animal; D010963:Plasmodium falciparum / Q000472:pathogenicity*; D011485:Protein Binding / Q000502:physiology; D015800:Protozoan Proteins / Q000032:analysis* / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D011817:Rabbits; D015398:Signal Transduction / Q000502:physiology; D019699:Thrombospondins / Q000032:analysis* / Q000502:physiology*
chemical_list: D000911:Antibodies, Monoclonal; D000953:Antigens, Protozoan; D006021:Glycophorins; D008565:Membrane Proteins; C487867:PTRAMP protein, Plasmodium; D015800:Protozoan Proteins; D019699:Thrombospondins; C065668:erythrocyte-binding antigen 175, Plasmodium; C065352:rhoptry associated protein, Plasmodium