Identification of a 67-amino-acid region of the Plasmodium falciparum variant surface antigen that binds chondroitin sulphate A and elicits antibodies reactive with the surface of placental isolates

Molecular Microbiology
Benoit GamainLouis H Miller

Abstract

The complications of malaria in pregnancy are caused by the massive sequestration of parasitized erythrocytes (PE) in the placenta. Placental isolates of Plasmodium falciparum are unusual in that they do not bind the primary microvasculature receptor CD36 but instead bind chondroitin sulphate A (CSA). Pregnant mothers develop antibodies that recognize placental variants worldwide, suggesting that a vaccine against malaria in pregnancy is possible. Some members of the Duffy binding-like gamma (DBL-gamma) domain of the large and diverse P. falciparum erythrocyte membrane protein-1 (PfEMP-1) family, when expressed on Chinese hamster ovary (CHO) cells, bind CSA. To characterize better the molecular requirements for DBL-gamma adhesion to CSA, we determined the binding of various DBL-gamma domains. Most DBL-gamma did not bind CSA, and no conserved region was identified that strictly differentiated binders from non-binders. Structure-function analysis of the FCR3-CSA DBL-gamma domain localized the minimal CSA binding region to a 67-residue fragment. This region was partially conserved among some binding sequences. Serum from a rabbit immunized with the minimal domain reacted with CSA-binding parasite lines, but not with non-CSA-adhere...Continue Reading

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Citations

Dec 27, 2005·Infection, Genetics and Evolution : Journal of Molecular Epidemiology and Evolutionary Genetics in Infectious Diseases·Cindy C Korir, Mary R Galinski
Jan 28, 2009·Nature Structural & Molecular Biology·Kavita SinghDavid N Garboczi
Nov 3, 2004·The Journal of Experimental Medicine·Ali SalantiThor G Theander
Jul 25, 2006·Infection and Immunity·Michael F DuffyStephen J Rogerson
Sep 5, 2009·The Journal of Clinical Investigation·Thomas E WellemsRick M Fairhurst
Mar 2, 2010·Trends in Parasitology·Madeleine DahlbäckAli Salanti
Jun 3, 2008·Transfusion clinique et biologique : journal de la Société française de transfusion sanguine·O Mercereau-PuijalonI Vigan-Womas
Jan 17, 2007·International Journal for Parasitology·Benoît GamainArtur Scherf
Nov 11, 2006·Microbes and Infection·Marion AvrilJürg Gysin
Jan 31, 2006·Molecular and Biochemical Parasitology·Jean-Philippe SemblatJ Alexandra Rowe
Dec 13, 2006·Brazilian Journal of Medical and Biological Research = Revista Brasileira De Pesquisas Médicas E Biológicas·F T M CostaJ Gysin

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