The semiconserved head structure of Plasmodium falciparum erythrocyte membrane protein 1 mediates binding to multiple independent host receptors

J Exp Med. 2000 Jul 3;192(1):1-10. doi: 10.1084/jem.192.1.1.

Abstract

Erythrocytes infected with mature forms of Plasmodium falciparum do not circulate but are withdrawn from the peripheral circulation; they are bound to the endothelial lining and to uninfected erythrocytes in the microvasculature. Blockage of the blood flow, hampered oxygen delivery, and severe malaria may follow if binding is excessive. The NH(2)-terminal head structure (Duffy binding-like domain 1 [DBL1alpha]-cysteine-rich interdomain region [CIDR1alpha]) of a single species of P. falciparum erythrocyte membrane protein 1 (PfEMP1) is here shown to mediate adherence to multiple host receptors including platelet-endothelial cell adhesion molecule 1 (PECAM-1)/CD31, the blood group A antigen, normal nonimmune immunoglobulin M, three virulence-associated receptor proteins, a heparan sulfate-like glucosaminoglycan, and CD36. DBL2delta was found to mediate additional binding to PECAM-1/CD31. The exceptional binding activity of the PfEMP1 head structure and its relatively conserved nature argues that it holds an important role in erythrocyte sequestration and therefore in the virulence of the malaria parasite.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ABO Blood-Group System / physiology
  • Animals
  • Binding Sites
  • CD36 Antigens / physiology
  • CHO Cells
  • Cell Adhesion
  • Cricetinae
  • Erythrocyte Membrane / parasitology*
  • Glycosylation
  • Humans
  • Immunoglobulin G / physiology
  • Immunoglobulin M / physiology
  • Intercellular Adhesion Molecule-1 / physiology
  • L Cells
  • Mice
  • Plasmodium falciparum / physiology*
  • Platelet Endothelial Cell Adhesion Molecule-1 / physiology
  • Protozoan Proteins / chemistry
  • Protozoan Proteins / physiology*
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / metabolism
  • Transfection

Substances

  • ABO Blood-Group System
  • CD36 Antigens
  • Immunoglobulin G
  • Immunoglobulin M
  • Platelet Endothelial Cell Adhesion Molecule-1
  • Protozoan Proteins
  • Recombinant Proteins
  • erythrocyte membrane protein 1, Plasmodium falciparum
  • Intercellular Adhesion Molecule-1