The C-terminal segment of the cysteine-rich interdomain of Plasmodium falciparum erythrocyte membrane protein 1 determines CD36 binding and elicits antibodies that inhibit adhesion of parasite-infected erythrocytes.
Attachment of erythrocytes infected by Plasmodium falciparum to receptors of the microvasculature is a major contributor to the pathology and morbidity associated with malaria. Adhesion is mediated by the P. falciparum erythrocyte membrane protein 1 (PfEMP-1), which is expressed at the surface of infected erythrocytes and is linked to both antigenic variation and cytoadherence. PfEMP-1 contains multiple adhesive modules, including the Duffy binding-like domain and the cysteine-rich interdomain region (CIDR). The interaction between CIDRalpha and CD36 promotes stable adherence of parasitized erythrocytes to endothelial cells. Here we show that a segment within the C-terminal region of CIDRalpha determines CD36 binding specificity. Antibodies raised against this segment can specifically block the adhesion to CD36 of erythrocytes infected with various parasite strains. Thus, small regions of PfEMP-1 that determine binding specificity could form suitable components of an antisequestration malaria vaccine effective against different parasite strains.
Mo
Min
M
School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551.
Lee
Hooi Chen
HC
Kotaka
Masayo
M
Niang
Makhtar
M
Gao
Xiaohong
X
Iyer
Jayasree Kaveri
JK
Lescar
Julien
J
Preiser
Peter
P
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution / Q000235:genetics; D000818:Animals; D000913:Antibodies, Protozoan / Q000276:immunology*; D018955:CD36 Antigens / Q000378:metabolism*; D002448:Cell Adhesion / Q000276:immunology*; D002460:Cell Line; D006224:Cricetinae; D004912:Erythrocytes / Q000469:parasitology*; D006801:Humans; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D010963:Plasmodium falciparum / Q000502:physiology; D011485:Protein Binding; D025941:Protein Interaction Mapping; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D015800:Protozoan Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D011995:Recombination, Genetic; D016415:Sequence Alignment
D000913:Antibodies, Protozoan; D018955:CD36 Antigens; D015800:Protozoan Proteins; C085731:erythrocyte membrane protein 1, Plasmodium falciparum