Thrombospondin related anonymous protein (TRAP) of Plasmodium falciparum binds specifically to sulfated glycoconjugates and to HepG2 hepatoma cells suggesting a role for this molecule in sporozoite invasion of hepatocytes.
Thrombospondin related anonymous protein (TRAP) of Plasmodium falciparum contains an amino acid motif based around the sequence WSPCSVTCG which is also found in region II of the circumsporozoite (CS) proteins of different species of Plasmodium. This amino acid motif confers on the CS protein the ability to bind specifically to sulfated glycoconjugates and to hepatocytes. This suggests that the interaction of CS protein with sulfated glycoconjugates on the surface of the hepatocytes may represent the first molecular event of sporozoite invasion of liver cells. Experimental evidence indicates that TRAP is localized both on the micronemes and on the surface of P. falciparum sporozoites implying that TRAP with its putative sulfated glycoconjugate binding motif may also be involved in recognition and/or entry of hepatocytes by the sporozoite. We show here that different TRAP constructs expressed in Escherichia coli bind to sulfogalactosyl-cerebrosides (sulfatides) and to the surface of HepG2 cells. These interactions are dependent on the presence of the conserved amino acid motif WSPCSVTCG within the sequences of the constructs and are completely inhibited by several sulfated glycoconjugates as well as by suramin, a polysulfonated drug with anti-protozoan activity. Moreover, sporozoite invasion of HepG2 cells is inhibited by antisera raised against these different TRAP constructs and by the presence of low concentrations of suramin. We concluded that TRAP may be one of the parasite encoded molecules in the host-parasite interaction that results in sporozoite invasion of hepatocytes.
Istituto di Parassitologia, Università di Roma, La Sapienza, P.A. Moro, Italy.
H M
HM
Müller
I
I
Reckmann
M R
MR
Hollingdale
H
H
Bujard
K J
KJ
Robson
A
A
Crisanti
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D006528:Carcinoma, Hepatocellular; D003001:Cloning, Molecular; D004277:DNA, Single-Stranded; D004926:Escherichia coli; D006001:Glycoconjugates / Q000737:chemistry / Q000378:metabolism*; D008099:Liver / Q000469:parasitology*; D008969:Molecular Sequence Data; D010963:Plasmodium falciparum / Q000378:metabolism* / Q000502:physiology; D010980:Platelet Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D015800:Protozoan Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D013464:Sulfuric Acids / Q000737:chemistry; D019699:Thrombospondins; D014407:Tumor Cells, Cultured
D004277:DNA, Single-Stranded; D006001:Glycoconjugates; D010980:Platelet Membrane Glycoproteins; D015800:Protozoan Proteins; D013464:Sulfuric Acids; D019699:Thrombospondins; C069428:thrombospondin-related adhesive protein, protozoan