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This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Gamain, B. Articles by Baruch, D. I. Search for Related Content PubMed PubMed Citation Articles by Gamain, B. Articles by Baruch, D. I. Related Collections Red Cells Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 May 2001, Vol. 97, No. 10, pp. 3268-3274 RED CELLS Modifications in the CD36 binding domain of the Plasmodium falciparum variant antigen are responsible for the inability of chondroitin sulfate A adherent parasites to bind CD36 Benoit Gamain, Joseph D. Smith, Louis H. Miller, and Dror I. Baruch From the Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD; and the Department of Pathology, Colorado State University, Fort Collins, CO. Adhesion of mature Plasmodium falciparum parasitized erythrocytes to microvascular endothelial cells or to placenta contributes directly to the virulence and severe pathology of P falciparum malaria. Whereas CD36 is the major endothelial receptor for microvasculature sequestration, infected erythrocytes adhering in the placenta bind chondroitin sulfate A (CSA) but not CD36. Binding to both receptors is mediated by different members of the large and diverse protein family P falciparum erythrocyte membrane protein-1 (PfEMP-1) and involves different regions of the molecule. The PfEMP-1-binding domain for CD36 resides in the cysteine-rich interdomain region 1 (CIDR-1). To explore why CSA-binding parasites do not bind CD36, CIDR-1 domains from CD36- or CSA-binding parasites were expressed in mammalian cells and tested for adhesion. Although CIDR-1 domains from CD36-adherent strains strongly bound CD36, those from CSA-adherent parasites did not. The CIDR-1 domain has also been reported to bind CSA. However, none of the CIDR-1 domains tested bound CSA. Chimeric proteins between CIDR-1 domains that bind or do not bind CD36 and mutagenesis experiments revealed that modifications in the minimal CD36-binding region (M2 region) are responsible for the inability of CSA-selected parasites to bind CD36. One of these modifications, mapped to a 3-amino acid substitution in the M2 region, ablated binding in one variant and largely reduced binding of another. These findings provide a molecular explanation for the inability of placental sequestered parasites to bind CD36 and provide additional insight into critical residues for the CIDR-1/CD36 interaction. © 2001 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. Mo, H. C. Lee, M. Kotaka, M. Niang, X. Gao, J. K. Iyer, J. Lescar, and P. Preiser 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 Infect. Immun., May 1, 2008; 76(5): 1837 - 1847. [Abstract] [Full Text] [PDF] J. G. Beeson, K. T. Andrews, M. Boyle, M. F. Duffy, E. K. Choong, T. J. Byrne, J. M. Chesson, A. M. Lawson, and W. Chai Structural Basis for Binding of Plasmodium falciparum Erythrocyte Membrane Protein 1 to Chondroitin Sulfate and Placental Tissue and the Influence of Protein Polymorphisms on Binding Specificity J. Biol. Chem., August 3, 2007; 282(31): 22426 - 22436. [Abstract] [Full Text] [PDF] A. Muthusamy, R. N. Achur, M. Valiyaveettil, S. V. Madhunapantula, I. Kakizaki, V. P. Bhavanandan, and C. D. Gowda Structural characterization of the bovine tracheal chondroitin sulfate chains and binding of Plasmodium falciparum-infected erythrocytes Glycobiology, July 1, 2004; 14(7): 635 - 645. [Abstract] [Full Text] [PDF] S. Gratepanche, B. Gamain, J. D. Smith, B. A. Robinson, A. Saul, and L. H. Miller Induction of crossreactive antibodies against the Plasmodium falciparum variant protein PNAS, October 28, 2003; 100(22): 13007 - 13012. [Abstract] [Full Text] [PDF] D. I. Baruch, B. Gamain, and L. H. Miller DNA Immunization with the Cysteine-Rich Interdomain Region 1 of the Plasmodium falciparum Variant Antigen Elicits Limited Cross-Reactive Antibody Responses Infect. Immun., August 1, 2003; 71(8): 4536 - 4543. [Abstract] [Full Text] [PDF] B. G. Yipp, S. M. Robbins, M. E. Resek, D. I. Baruch, S. Looareesuwan, and M. Ho Src-family kinase signaling modulates the adhesion of Plasmodium falciparum on human microvascular endothelium under flow Blood, April 1, 2003; 101(7): 2850 - 2857. [Abstract] [Full Text] [PDF] B. G. Yipp, D. I. Baruch, C. Brady, A. G. Murray, S. Looareesuwan, P. Kubes, and M. Ho Recombinant PfEMP1 peptide inhibits and reverses cytoadherence of clinical Plasmodium falciparum isolates in vivo Blood, January 1, 2003; 101(1): 331 - 337. [Abstract] [Full Text] [PDF] B. Gamain, S. Gratepanche, L. H. Miller, and D. I. Baruch Molecular basis for the dichotomy in Plasmodium falciparum adhesion to CD36 and chondroitin sulfate A PNAS, July 23, 2002; 99(15): 10020 - 10024. [Abstract] [Full Text] [PDF] D. J. Weatherall, L. H. Miller, D. I. Baruch, K. Marsh, O. K. Doumbo, C. Casals-Pascual, and D. J. Roberts Malaria and the Red Cell Hematology, January 1, 2002; 2002(1): 35 - 57. [Abstract] [Full Text]

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