Interaction of Plasmodium falciparum knob-associated histidine-rich protein (KAHRP) with erythrocyte ankyrin R is required for its attachment to the erythrocyte membrane

Biochim Biophys Acta. 2014 Jan;1838(1 Pt B):185-92. doi: 10.1016/j.bbamem.2013.09.014. Epub 2013 Sep 30.


The malaria parasite Plasmodium falciparum exports a large number of proteins into the erythrocyte cytoplasm during the asexual intraerythrocytic stage of its life cycle. A subset of these proteins interacts with erythrocyte membrane skeletal proteins and grossly alters the structure and function of the membrane. Several of the exported proteins, such as PfEMP1, PfEMP3, RESA and KAHRP, interact with the preponderant erythrocyte skeleton protein, spectrin. Here we have searched for possible interaction of these four malaria proteins with another major erythrocyte skeleton protein, ankyrin R. We have shown that KAHRP, but none of the other three, binds to ankyrin R. We have mapped the binding site for ankyrin R to a 79-residue segment of the KAHRP sequence, and the reciprocal binding site for KAHRP in ankyrin R to a subdomain (D3) of the 89kDa ankyrin R membrane-binding domain. Interaction of intact ankyrin R with KAHRP was inhibited by the free D3 subdomain. When, moreover, red cells loaded with the soluble D3 subdomain were infected with P. falciparum, KAHRP secreted by the intraerythrocytic parasite no longer migrated to the host cell membrane, but remained diffusely distributed throughout the cytosol. Our findings suggest a potentially important role for interaction of KAHRP with red cell membrane skeleton in promoting the adhesion of malaria-infected red cells to endothelial surfaces, a central element in the pathophysiology of malaria.

Keywords: Ankyrin R; Cytoskeletal proteins; KAHRP; Malaria; Red cell.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Ankyrins / chemistry*
  • Ankyrins / genetics
  • Ankyrins / metabolism
  • Binding Sites
  • Erythrocytes / drug effects
  • Erythrocytes / metabolism
  • Erythrocytes / parasitology*
  • Escherichia coli / genetics
  • Escherichia coli / metabolism
  • Gene Expression
  • Host-Parasite Interactions
  • Humans
  • Membrane Proteins / chemistry
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Oligopeptides / chemistry*
  • Oligopeptides / genetics
  • Oligopeptides / metabolism
  • Oligopeptides / pharmacology
  • Peptides / chemistry*
  • Peptides / genetics
  • Peptides / metabolism
  • Plasmodium falciparum / chemistry
  • Plasmodium falciparum / drug effects
  • Plasmodium falciparum / growth & development
  • Plasmodium falciparum / metabolism*
  • Protein Binding
  • Protein Isoforms / chemistry
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Protein Structure, Tertiary
  • Protozoan Proteins / chemistry*
  • Protozoan Proteins / genetics
  • Protozoan Proteins / metabolism
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Recombinant Proteins / pharmacology


  • Ankyrins
  • EMP3 protein, Plasmodium falciparum
  • Membrane Proteins
  • Oligopeptides
  • Peptides
  • Protein Isoforms
  • Protozoan Proteins
  • Recombinant Proteins
  • erythrocyte membrane protein 1, Plasmodium falciparum
  • knob protein, Plasmodium falciparum
  • ring-infected erythrocyte surface antigen (RESA), Plasmodium falciparum