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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

Min Mo,^1, Hooi Chen Lee,¹ Masayo Kotaka,¹ Makhtar Niang,¹ Xiaohong Gao,¹ Jayasree Kaveri Iyer,¹ Julien Lescar,^1,2* and Peter Preiser^1*

School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551,¹ AFMB, CNRS UMR6098, Marseille, France²

Received 3 April 2007/ Returned for modification 16 May 2007/ Accepted 13 February 2008

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 CIDR and CD36 promotes stable adherence of parasitized erythrocytes to endothelial cells. Here we show that a segment within the C-terminal region of CIDR 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.

Published ahead of print on 25 February 2008.

Editor: J. F. Urban, Jr.

Present address: Center for Advanced Research in Biotechnology, W.M. Keck Laboratory for Structural Biology, University of Maryland Biotechnology Institute, Rockville, MD 20850.