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Identification of Plasmodium falciparum Protein That Mediates the Adherence of Infected Red Blood Cells to Placental Chondroitin Sulfate Receptor
Author(s) -
Prakasha Gowda A.S,
Achur Rajeshwara N,
Gowda D. Channe
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a913-b
Subject(s) - plasmodium falciparum , chemistry , biochemistry , chondroitin sulfate , sulfation , chondroitin sulfate proteoglycan , placenta , receptor , oligosaccharide , glycosaminoglycan , biology , fetus , immunology , pregnancy , genetics , malaria
In pregnant women infected with Plasmodium falciparum , the infected red blood cells (IRBCs) sequester in the placenta contributing to poor pregnancy outcomes. The placental adherent IRBCs have been shown to bind to chondroitin 4‐sulfate (C4S). We have previously shown that a uniquely low‐sulfated chondroitin sulfate proteoglycan (CSPG) is the receptor for IRBC adherence in the placenta. A C4S dodecasaccharide is the minimal chain length required for IRBC adherence and the optimal binding requires a minimum of two 4‐sulfated disaccharide moieties. Structure‐adherence activity analyses indicated that sulfate and hydroxyl groups at C‐4 of N ‐acetylgalactosamine and the carboxyl group of uronic acid are critical for IRBC binding, whereas N ‐acetyl groups are not essential. Based on these results, we prepared a photoactive derivative of oligosaccharide for the identification of the parasite adhesive protein expressed on the surface of IRBCs. The probe was prepared by partially replacing N ‐acetyl groups of C4S oligosaccharides with iodinatable azido group‐containing benzoyl moieties. The photoactive oligosaccharide derivative was radiolabeled with 125 I and cross‐linked to C4S‐adherent IRBCs by UV irradiation. SDS‐PAGE analysis of the IRBC lysate showed cross‐linking of the probe to a novel parasite protein. This cross‐linking was inhibited by the unlabeled probe and by underivatized dodecasaccharides. To identify the parasite protein, we derivatized further the photoaffinity probe with biotin hydrazide at the reducing end and used for the cross‐linking experiments. We are currently purifying the adhesive protein using immobilized avidin for characterization by mass spectrometry. Supported by the grant AI45086 from NIAID, NIH.