A malaria invasion receptor, the 175-kilodalton erythrocyte binding antigen of Plasmodium falciparum recognizes the terminal Neu5Ac(alpha 2-3)Gal- sequences of glycophorin A

J Cell Biol. 1992 Feb;116(4):901-9. doi: 10.1083/jcb.116.4.901.


Plasmodium falciparum malaria parasites invade human erythrocytes by means of a parasite receptor for erythrocytes, the 175-kD erythrocyte binding antigen (EBA-175). Similar to invasion efficiency, binding requires N-acetylneuraminic acid (Neu5Ac) on human erythrocytes, specifically the glycophorins. EBA-175 bound to erythrocytes with receptor-like specificity and was saturable. The specificity of EBA-175 binding was studied to determine if its binding is influenced either by simple electrostatic interaction with the negatively charged Neu5Ac (on the erythrocyte surface); or if Neu5Ac indirectly affected the conformation of an unknown ligand, or if Neu5Ac itself in specific linkage and carbohydrate composition was the primary ligand for EBA-175 as demonstrated for hemagglutinins of influenza viruses. Most Neu5Ac on human erythrocytes is linked to galactose by alpha 2-3 and alpha 2-6 linkages on glycophorin A. Soluble Neu5Ac by itself in solution did not competitively inhibit the binding of EBA-175 to erythrocytes, suggesting that linkage to an underlying sugar is required for binding in contrast to charge alone. Binding was competitively inhibited only by Neu5Ac(alpha 2-3)Gal-containing oligosaccharides. Similar oligosaccharides containing Neu5Ac(alpha 2-6)Gal-linkages had only slight inhibitory effects. Binding inhibition assays with modified sialic acids and other saccharides confirmed that oligosaccharide composition and linkage were primary factors for efficient binding. EBA-175 bound tightly enough to glycophorin A that the complex could be precipitated with an anti-glycophorin A monoclonal antibody. Selective cleavage of O-linked tetrasaccharides clustered at the NH2 terminus of glycophorin A markedly reduced binding in inhibition studies. We conclude that the Neu5Ac(a2,3)-Gal- determinant on O-linked tetrasaccharides of glycophorin A appear to be the preferential erythrocyte ligand for EBA-175.

MeSH terms

  • Animals
  • Antigens, Protozoan / chemistry
  • Antigens, Protozoan / metabolism*
  • Antigens, Surface / chemistry
  • Antigens, Surface / metabolism
  • Binding, Competitive
  • Carbohydrate Conformation
  • Carbohydrate Sequence
  • Carrier Proteins / chemistry
  • Carrier Proteins / metabolism*
  • Erythrocytes / metabolism*
  • Glycophorins / chemistry
  • Glycophorins / metabolism*
  • Humans
  • Molecular Sequence Data
  • N-Acetylneuraminic Acid
  • Oligosaccharides / chemistry
  • Oligosaccharides / metabolism
  • Oligosaccharides / pharmacology
  • Periodic Acid / pharmacology
  • Plasmodium falciparum / immunology*
  • Protozoan Proteins*
  • Sialic Acids / chemistry
  • Sialic Acids / metabolism
  • Sialic Acids / pharmacology


  • Antigens, Protozoan
  • Antigens, Surface
  • Carrier Proteins
  • Glycophorins
  • Oligosaccharides
  • Protozoan Proteins
  • Sialic Acids
  • erythrocyte-binding antigen 175, Plasmodium
  • Periodic Acid
  • N-Acetylneuraminic Acid