The semiconserved head structure of Plasmodium falciparum erythrocyte membrane protein 1 mediates binding to multiple independent host receptors.
Erythrocytes infected with mature forms of Plasmodium falciparum do not circulate but are withdrawn from the peripheral circulation; they are bound to the endothelial lining and to uninfected erythrocytes in the microvasculature.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.
Chen
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Q
Microbiology and Tumor Biology Center, Karolinska Institutet, The Swedish Institute for Infectious Disease Control, S-171 77 Stockholm, Sweden.
Heddini
A
A
Barragan
A
A
Fernandez
V
V
Pearce
S F
SF
Wahlgren
M
M
D000017:ABO Blood-Group System / Q000502:physiology; D000818:Animals; D001665:Binding Sites; D018955:CD36 Antigens / Q000502:physiology; D016466:CHO Cells; D002448:Cell Adhesion; D006224:Cricetinae; D004910:Erythrocyte Membrane / Q000469:parasitology*; D006031:Glycosylation; D006801:Humans; D007074:Immunoglobulin G / Q000502:physiology; D007075:Immunoglobulin M / Q000502:physiology; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology; D007739:L Cells; D051379:Mice; D010963:Plasmodium falciparum / Q000502:physiology*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000502:physiology; D015800:Protozoan Proteins / Q000737:chemistry / Q000502:physiology*; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D014162:Transfection
D000017:ABO Blood-Group System; D018955:CD36 Antigens; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D015800:Protozoan Proteins; D011994:Recombinant Proteins; C085731:erythrocyte membrane protein 1, Plasmodium falciparum; D018799:Intercellular Adhesion Molecule-1