Structural interactions in chondroitin 4-sulfate mediated adherence of Plasmodium falciparum infected erythrocytes in human placenta during pregnancy-associated malaria.
Structural interactions in chondroitin 4-sulfate mediated adherence of Plasmodium falciparum infected erythrocytes in human placenta during pregnancy-associated malaria.
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DOI：
10.1021/bi801643m
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发表时间：
2008-11-25
期刊：
影响因子：
2.9
通讯作者：
Gowda, D. Channe
中科院分区：
文献类型：
--
作者：
Achur, Rajeshwara N.;Kakizaki, Ikuko;Goel, Suchi;Kojima, Kaoru;Madhunapantula, SubbaRao V.;Goyal, Atul;Ohta, Misato;Kumar, Sanjeev;Takagaki, Keiichi;Gowda, D. Channe
妊娠期间感染恶性疟原虫导致感染的红细胞（IRBC）粘附在胎盘中，导致妊娠相关疟疾，并在母亲和胎儿中引起严重的健康并发症。胎盘中极低硫酸化硫酸软骨素蛋白聚糖（CSPG）的4-硫酸软骨素（C4 S）链介导IRBC粘附。虽然已知部分硫酸化但不完全硫酸化的C4 S有效地结合IRBC，但涉及的结构相互作用仍然不清楚并且不完全理解。在这项研究中，不同硫酸根含量和大小的结构确定的C4 S寡糖被评估其抑制来自不同恶性疟原虫菌株的IRBC与从胎盘纯化的CSPG结合的能力。结果清楚地表明，对于研究的所有寄生虫菌株，十二糖是IRBC有效粘附于CSPG所需的最小链长，并且在该最小结构基序内的两个4-硫酸化二糖足以实现最大结合。总之，这些数据首次表明，IRBC粘附的C4 S结构要求是寄生虫菌株无关的。我们还表明，羧基上的非还原性端葡萄糖醛酸在十二糖基序是重要的IRBC结合。因此，在含有末端4，5-不饱和葡萄糖醛酸的寡糖中，由于羧基的空间取向改变，非还原性末端二糖部分不与IRBC相互作用。在这种C4 S寡糖中，14聚体而不是12聚体构成抑制IRBC与胎盘CSPG结合的最小基序。这些数据对胎盘型疟疾治疗药物和疫苗的开发和评价具有重要意义。
Infection with Plasmodium falciparum during pregnancy results in the adherence of infected red blood cells (IRBCs) in placenta, causing pregnancy-associated malaria with severe health complications in mothers and fetuses. The chondroitin 4-sulfate (C4S) chains of very low-sulfated chondroitin sulfate proteoglycans (CSPGs) in placenta mediate the IRBC adherence. While it is known that partially sulfated but not fully sulfated C4S effectively binds IRBCs, structural interactions involved remain unclear and are incompletely understood. In this study, structurally defined C4S oligosaccharides of varying sulfate contents and sizes were evaluated for their ability to inhibit the binding of IRBCs from different P. falciparum strains to CSPG purified from placenta. The results clearly show that, with all parasite strains studied, dodecasaccharide is the minimal chain length required for the efficient adherence of IRBCs to CSPG and two 4-sulfated disaccharides within this minimal structural motif are sufficient for maximal binding. Together these data demonstrate for the first time that the C4S structural requirement for IRBC adherence is parasite strain-independent. We also show that the carboxyl group on nonreducing end glucuronic acid in dodecasaccharide motif is important for IRBC binding. Thus, in oligosaccharides containing terminal 4,5-unsaturated glucuronic acid, the nonreducing end disaccharide moiety does not interact with IRBCs due to the altered spatial orientation of carboxyl group. In such C4S oligosaccharides, 14 mer but not 12 mer constitutes the minimal motif for inhibition of IRBC binding to placental CSPG. These data have important implications for the development and evaluation of therapeutics and vaccine for placental malaria.
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DOI：
10.1080/00021369.1989.10869625
发表时间：
1989-08-01
期刊：
AGRICULTURAL AND BIOLOGICAL CHEMISTRY
影响因子：
--
作者：
HAMAI, A;MORIKAWA, K;TOKUYASU, K
通讯作者：
TOKUYASU, K
影响因子：
3.1
作者：
Avril, Marion;Kulasekara, Bridget R.;Smith, Joseph D.
通讯作者：
Smith, Joseph D.
影响因子：
4.8
作者：
Alkhalil, A;Achur, RN;Gowda, DC
通讯作者：
Gowda, DC
影响因子：
3.1
作者：
Heddini, A;Pettersson, F;Marsh, K
通讯作者：
Marsh, K
影响因子：
3
作者：
Resende M;Nielsen MA;Dahlbäck M;Ditlev SB;Andersen P;Sander AF;Ndam NT;Theander TG;Salanti A
通讯作者：
Salanti A