The Semiconserved Head Structure of Plasmodium falciparum Erythrocyte Membrane Protein 1 Mediates Binding to Multiple Independent Host Receptors

doi:10.1084/jem.192.1.1

Published online 3 July 2000.

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© The Rockefeller University Press, 0022-1007/2000/7/1/ $5.00
The Journal of Experimental Medicine, Volume 192, Number 1, July 3, 2000 1-10

Original Article

The Semiconserved Head Structure of Plasmodium falciparum Erythrocyte Membrane Protein 1 Mediates Binding to Multiple Independent Host Receptors

Qijun Chen^a, Andreas Heddini^a, Antonio Barragan^a, Victor Fernandez^a, S. Frieda A. Pearce^b, and Mats Wahlgren^a

^a Microbiology and Tumor Biology Center, Karolinska Institutet, The Swedish Institute for Infectious Disease Control, S-171 77 Stockholm, Sweden
^b Department of Medicine, Division of Hematology-Oncology, Cornell University, Medical College, New York, New York 10021
Microbiology and Tumor Biology Center, Karolinska Institutet, The Swedish Institute for Infectious Disease Control, Box 280, S-171 77 Stockholm, Sweden.46-8-31052546-8-4572510

mats.wahlgren{at}smi.ki.se

Erythrocytes infected with mature forms of Plasmodium falciparumdo not circulate but are withdrawn from the peripheral circulation;they are bound to the endothelial lining and to uninfected erythrocytesin the microvasculature. Blockage of the blood flow, hamperedoxygen delivery, and severe malaria may follow if binding isexcessive. The NH₂-terminal head structure (Duffy binding–likedomain 1 [DBL1 ${alpha}$ ]–cysteine-rich interdomain region [CIDR1 ${alpha}$ ])of a single species of P. falciparum erythrocyte membrane protein1 (PfEMP1) is here shown to mediate adherence to multiple hostreceptors including platelet-endothelial cell adhesion molecule1 (PECAM-1)/CD31, the blood group A antigen, normal nonimmuneimmunoglobulin M, three virulence-associated receptor proteins,a heparan sulfate–like glucosaminoglycan, and CD36. DBL2 ${delta}$ was found to mediate additional binding to PECAM-1/CD31. Theexceptional binding activity of the PfEMP1 head structure andits relatively conserved nature argues that it holds an importantrole in erythrocyte sequestration and therefore in the virulenceof the malaria parasite.

Key Words: malaria • sequestration • cytoadherence • rosetting • ligand

Abbreviations used in this paper: aa, amino acid(s); ALP, alkalinephosphatase; CHO, Chinese hamster ovary; CIDR, cysteine-richinterdomain region; DBL, Duffy binding–like; GAG, glycosaminoglycan;GST, glutathione S-transferase; HS, heparan sulfate; ICAM-1,intracellular adhesion molecule 1; PECAM-1, platelet-endothelialcell adhesion molecule 1; PfEMP1, P. falciparum erythrocytemembrane protein 1; pRBC, parasited RBC; RT, reverse transcriptase.

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