A thrombospondin structural repeat containing rhoptry protein fromPlasmodium falciparummediates 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.

Motility precedes egress of malaria parasites from oocysts

“…However, the calculated isoelectric point (pI) of the CTD of TRP1 varied widely between homologues from different Plasmodium species and indicated no enrichment for acidic amino acids (Figure 1D). Due to the overall similarity to TRAP-family proteins, we grouped TRP1 together with TRAMP (Thompson et al, 2004; Siddiqui et al, 2013), TRSP (Labaied et al, 2007) and SSP3 (Harupa et al, 2014) in the family of TRAP-related proteins that have a potential cytoplasmic tail domain (CTD) but lack the conserved tryptophan (Figure 1A). Homologues of TRP1 can be found in all Plasmodium species, but we could not identify homologues in other apicomplexans.…”

Malaria Parasites: The Great Escape

“…Thrombospondin type-1 repeat (TSR) domains and von Willebrand factor (vWF)-like A domains are present in the CS protein, thrombospondin-related anonymous protein (TRAP) (178, 179), CS protein TRAP-related protein (CTRP) sporozoite surface protein (180), secreted protein with an altered thrombospondin (SPATR) (181), and thrombospondin-related apical merozoite protein (TRAMP) (182). These molecules are involved in different stages of parasite development, in sporozoite and merozoite motility, and in invasion of mosquito midguts, salivary glands, hepatocytes, and RBC.…”

Red cell receptors as access points for malaria infection

“…CD55 and ICAM-4 are RBC receptors without known parasite ligands identified through forward genetics [46] and parasite inhibition studies [47], respectively (Table 2). Conversely, parasite ligands without known receptors include PfMSPDBL 1 & 2 [49], PfRh2 [50], PfEBA-181 [48], and PfTRAMP (Table 2) [51]. These proteins remain an area of active study to fully define the range of RBC interactions available to the malaria parasite.…”