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The A4VAR is a variant antigen expressed by a clonal line that binds CD36 and intercellular adhesion molecule-1, ICAM-1. We have cloned and sequenced the extracellular domain coded by the A4var gene. To probe the relationship between A4var expression and parasite adhesion to ICAM-1, var mRNA and protein expression were analyzed in an enriched population of A4 parasites that displayed higher ICAM-1 binding. By Northern analyses, A4var was the predominant var message and antisera raised against a recombinant A4VAR protein reacted with the majority of infected erythrocytes, reinforcing previous conclusions that A4VAR binds ICAM-1. A4VAR contains five Duffy-binding like (DBL) domains, and two cysteine-rich interdomain regions (CIDR) domains. DBL and CIDR domains from A4VAR were expressed in mammalian cells to determine which regions mediate binding to CD36 and ICAM-1. Using several different binding assays, the A4VAR CIDR1 was the only domain found to bind CD36. In contrast, the same assays were unable to identify the ICAM-1 binding domain in A4VAR. This is the first time that each of the DBL and CIDR domains from a Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) have been systematically expressed and tested for binding. These results confirm that CIDR1 is sufficient to bind CD36 without any apparent contribution from other domains.

Type

Journal article

Journal

Mol Biochem Parasitol

Publication Date

30/11/1998

Volume

97

Pages

133 - 148

Keywords

Animals, Antibodies, Protozoan, Antibody Specificity, Antigens, CD36, Antigens, Protozoan, Base Sequence, CHO Cells, COS Cells, Cloning, Molecular, Cricetinae, Erythrocyte Membrane, Genes, Protozoan, Intercellular Adhesion Molecule-1, Molecular Sequence Data, Protein Binding, Protozoan Proteins, Recombinant Proteins