The structural motif in chondroitin sulfate for adhesion of Plasmodium falciparum-infected erythrocytes comprises disaccharide units of 4-O-sulfated and non-sulfated N-acetylgalactosamine linked to glucuronic acid

被引:57
作者
Chai, WG [1 ]
Beeson, JG
Lawson, AM
机构
[1] Northwick Pk Hosp & Clin Res Ctr, Imperial Coll Sch Med, MRC, Glycosci Lab, Harrow HA1 3UJ, Middx, England
[2] Univ Melbourne, Royal Melbourne Hosp, Dept Med, Parkville, Vic 3050, Australia
关键词
D O I
10.1074/jbc.M111401200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
An important characteristic of malaria parasite Plasmodium falciparum-infected red blood cells (IRBCs) is their ability to adhere to host endothelial cells and accumulate in various organs. Sequestration of IRBCs in the placenta, associated with excess perinatal and maternal mortality, is mediated in part by adhesion of parasites to the glycosaminoglyean chondroitin sulfate A (CSA) present on sncytiotrophoblasts lining the placental blood spaces. To define key structural features for parasite interactions, we isolated from CSA oligosaccharide fractions and established by electrospray mass spectrometry and high performance liquid chromatography disaccharide composition analysis their differing chain length, sulfate content, and sulfation pattern. Testing these defined oligosaccharide fragments for their ability to inhibit IRBC adhesion to immobilized CSA revealed the importance of non-sulfated disaccharide units in combination with 4-O-sulfated disaccharides for interaction with IRBCs. Selective removal of 6-O-sulfates from oligo- and polysaccharides to increase the proportion of non-sulfated disaccharides enhanced activity, indicating that 6-O-sulfation interferes with the interaction of CSA with IRBCs. Dodecasaccharides with four or five 4-O-sulfated and two or one non-sulfated disaccharide units, respectively, comprise the minimum chain length for effective interaction with IRBCs. Comparison of the activities of CSA and CSB oligo- and polysaccharides with a similar sulfation pattern and content achieved from partial desulfation demonstrated that glucuronic acid rather than iduronic acid residues are important for IRBC binding.
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页码:22438 / 22446
页数:9
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