Plasmodium falciparum erythrocyte membrane protein 1 is anchored to the actin-spectrin junction and knob-associated histidine-rich protein in the erythrocyte skeleton

Mol Biochem Parasitol. 2000 May;108(2):237-47. doi: 10.1016/s0166-6851(00)00227-9.


A distinctive pathological feature of Plasmodium falciparum malaria is the endothelial attachment of erythrocytes infected with mature asexual-stage parasites in microvessels of the major organs. Electron-dense protrusions described as knobs are displayed on the surface of parasitized erythrocytes and act as attachment points in cytoadherence. Parasite-encoded knob-associated histidine-rich protein (KAHRP) is a major component of knobs found on the cytoplasmic side of the host cell membrane. P. falciparum erythrocyte membrane protein 1 (PfEMP1) is a family of parasite-encoded cytoadherence receptors localized to knobs on the surface of parasitized erythrocytes. Despite its high antigenic diversity, PfEMP1 has a remarkably conserved cytoplasmic domain. We demonstrate in this study that the cytoplasmic domain of PfEMP1 (VAR(CD)) binds to host spectrin and actin and to full-length KAHRP in vitro. Apparent dissociation constants determined for VAR(CD)/F-actin and VAR(CD)/KAHRP interactions are 44.9+/-6.4 and 10. 7+/-2.2 nM, respectively. Further, we provide evidence that KAHRP polypeptides self-associate in solution to form structures similar to knobs and show binding of self-associated KAHRP clusters to spectrin-actin-protein 4.1 complexes. Findings in this study suggest that PfEMP1 is localized to the knob in P. falciparum-infected erythrocytes by binding to the host spectrin-actin junction and to self-associated KAHRP through its conserved cytoplasmic domain.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Actins / metabolism*
  • Animals
  • Cell Cycle Proteins / chemistry
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Cloning, Molecular
  • Erythrocyte Membrane / metabolism*
  • Molecular Sequence Data
  • Peptides / chemistry*
  • Peptides / genetics
  • Peptides / metabolism*
  • Plasmodium falciparum / metabolism*
  • Plasmodium falciparum / pathogenicity
  • Plasmodium falciparum / physiology
  • Protozoan Proteins / chemistry
  • Protozoan Proteins / genetics
  • Protozoan Proteins / metabolism*
  • Saccharomyces cerevisiae Proteins*
  • Spectrin / metabolism


  • Actins
  • Cell Cycle Proteins
  • MAK16 protein, S cerevisiae
  • Peptides
  • Protozoan Proteins
  • Saccharomyces cerevisiae Proteins
  • erythrocyte membrane protein 1, Plasmodium falciparum
  • knob protein, Plasmodium falciparum
  • Spectrin

Associated data

  • GENBANK/AF234186
  • GENBANK/AF234187