Identification of Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) as the rosetting ligand of the malaria parasite P. falciparum

J Exp Med. 1998 Jan 5;187(1):15-23. doi: 10.1084/jem.187.1.15.

Abstract

Severe Plasmodium falciparum malaria is characterized by excessive sequestration of infected and uninfected erythrocytes in the microvasculature of the affected organ. Rosetting, the adhesion of P. falciparum-infected erythrocytes to uninfected erythrocytes is a virulent parasite phenotype associated with the occurrence of severe malaria. Here we report on the identification by single-cell reverse transcriptase PCR and cDNA cloning of the adhesive ligand P. falciparum erythrocyte membrane protein 1 (PfEMP1). Rosetting PfEMP1 contains clusters of glycosaminoglycan-binding motifs. A recombinant fusion protein (Duffy binding-like 1-glutathione S transferase; Duffy binding-like-1-GST) was found to adhere directly to normal erythrocytes, disrupt naturally formed rosettes, block rosette reformation, and bind to a heparin-Sepharose matrix. The adhesive interactions could be inhibited with heparan sulfate or enzymes that remove heparan sulfate from the cell surface whereas other enzymes or similar glycosaminoglycans of a like negative charge did not affect the binding. PfEMP1 is suggested to be the rosetting ligand and heparan sulfate, or a heparan sulfate-like molecule, the receptor both for PfEMP1 binding and naturally formed erythrocyte rosettes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Binding Sites
  • Blood Proteins / genetics
  • Blood Proteins / physiology*
  • Cloning, Molecular
  • DNA Primers / genetics
  • DNA, Complementary / genetics
  • Erythrocyte Membrane / parasitology*
  • Glycosaminoglycans / metabolism
  • Heparitin Sulfate / metabolism
  • Humans
  • In Vitro Techniques
  • Ligands
  • Malaria, Falciparum / blood
  • Malaria, Falciparum / parasitology
  • Membrane Proteins / genetics
  • Membrane Proteins / physiology*
  • Molecular Sequence Data
  • Plasmodium falciparum / genetics
  • Plasmodium falciparum / pathogenicity*
  • Plasmodium falciparum / physiology*
  • Polymerase Chain Reaction
  • Protein Binding
  • Protozoan Proteins / genetics
  • Protozoan Proteins / physiology*
  • Recombinant Fusion Proteins / genetics
  • Rosette Formation

Substances

  • Blood Proteins
  • DNA Primers
  • DNA, Complementary
  • Glycosaminoglycans
  • Ligands
  • Membrane Proteins
  • Protozoan Proteins
  • Recombinant Fusion Proteins
  • erythrocyte membrane protein 1, Plasmodium falciparum
  • Heparitin Sulfate

Associated data

  • GENBANK/AF003473