Plasmodium falciparum histidine-rich protein 1 associates with the band 3 binding domain of ankyrin in the infected red cell membrane

Abstract

Infection of erythrocytes by the malaria parasite Plasmodium falciparum results in the export of several parasite proteins into the erythrocyte cytoplasm. Changes occur in the infected erythrocyte due to altered phosphorylation of proteins and to novel interactions between host and parasite proteins, particularly at the membrane skeleton. In erythrocytes, the spectrin based red cell membrane skeleton is linked to the erythrocyte plasma membrane through interactions of ankyrin with spectrin and band 3. Here we report an association between the P. falciparum histidine-rich protein (PfHRP1) and phosphorylated proteolytic fragments of red cell ankyrin. Immunochemical, biochemical and biophysical studies indicate that the 89 kDa band 3 binding domain and the 62 kDa spectrin-binding domain of ankyrin are co-precipitated by mAb 89 against PfHRP1, and that native and recombinant ankyrin fragments bind to the 5' repeat region of PfHRP1. PfHRP1 is responsible for anchoring the parasite cytoadherence ligand to the erythrocyte membrane skeleton, and this additional interaction with ankyrin would strengthen the ability of PfEMP1 to resist shear stress.

Plasmodium falciparum STEVOR phosphorylation regulates host erythrocyte deformability enabling malaria parasite transmission

“…10,11,45,46 The rise in the knob density in mature asexual stages results in the increased number of vertical constraints between the spectrin network and the lipid bilayer, which further stiffens the membrane. 47 In GIEs, KAHRP and PfEMP1 are not expressed 48,49 and STEVORs may perform an analogous role by increasing vertical constraints between the cytoskeleton and the lipid bilayer.…”

Cytoskeleton of Apicomplexan Parasites

“…These structural alterations contribute to sequestration of infected red cells in organ capillaries, preventing their circulation and exposure to the spleen (107). The Plasmodium proteins RESA, MESA, and HRP-1 are anchored to the red cell membrane by association with spectrin, band 4.1, and the band 3 binding domain of ankyrin, respectively (17,94,97,122). P. falciparum growth is decreased in human erythrocytes containing abnormal spectrin or band 4.1 (142).…”

PfEMP1 expression is reduced on the surface of knoblessPlasmodium falciparuminfected erythrocytes

“…KAHRP interacts directly with both the cytoplasmic tail of PfEMP1 as well as components of a modified IE cytoskeleton (Magowan et al, 2000;Oh et al, 2000;Waller et al, 1999;Waller et al, 2002). These interactions are thought to transmit shear stress forces developed during adhesion under conditions of physiological flow across the entire cytoskeleton of IEs (Crabb et al, 1997).…”