The glycophorin CN-linked glycan is a critical component of the ligand for the Plasmodium falciparum erythrocyte receptor BAEBL
The glycophorin CN-linked glycan is a critical component of the ligand for the Plasmodium falciparum erythrocyte receptor BAEBL
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DOI：
10.1073/pnas.0510648103
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发表时间：
2006-02-14
影响因子：
11.1
通讯作者：
Miller, LH
中科院分区：
文献类型：
--
作者：
Mayer, DCG;Jiang, LB;Miller, LH
间日疟原虫使用达菲结合样受体（DBL）家族的一个成员侵入红细胞，并且在西非没有发现，因为西非缺少其红细胞配体达菲血型抗原。相反，恶性疟原虫表达DBL家族的四个成员，并且值得注意的是，这些受体中的两个（BAEBL和JESEBL）的单点突变与完全不同的红细胞配体结合，大大扩展了恶性疟原虫可以侵入的红细胞的范围。在这篇文章中，我们描述了一种结合血型糖蛋白C的BAEBL变异体（VSTK）的结合特异性的分子基础。我们证明，可溶性血型糖蛋白C完全阻断BAEBL（VSTK）与人红细胞的结合，需要0.7 μ M的50%抑制，血型糖蛋白A阻断红细胞结合抗原175与红细胞的结合所需的浓度相似。BAEBL（VSTK）不与表达截短型血型糖蛋白C的Gerbich阴性红细胞结合，因为它缺乏外显子3。Gerbich阴性血型糖蛋白C的N-连接寡糖具有与野生型血型糖蛋白C显著不同的组成。此外，从野生型血型糖蛋白C中去除Winked寡糖消除了其抑制BAEBL（VSTK）与红细胞结合的能力。这些发现与BAEBL（VSTK）的配体部分是N-连接的寡糖一致，并表明BAEBL中的单点突变允许恶性疟原虫识别不同红细胞表面糖蛋白或糖脂上的寡糖，大大增加了其侵袭范围。
Plasmodium vivax uses a single member of the Duffy binding-like (DBL) receptor family to invade erythrocytes and is not found in West Africa where its erythrocyte ligand, the Duffy blood group antigen, is missing. In contrast, Plasmodium falciparum expresses four members of the DBL family, and remarkably, single-point mutations of two of these receptors (BAEBL and JESEBL) bind to entirely different erythrocyte ligands, greatly expanding the range of erythrocytes that A falciparum can invade. in this article, we describe the molecular basis of the binding specificity for one BAEBL variant (VSTK) that binds to glycophorin C. We demonstrate that soluble glycophorin C completely blocks the binding of BAEBL (VSTK) to human erythrocytes, requiring 0.7 mu M for 50% inhibition, a concentration similar to that required by glycophorin A to block the binding of erythrocyte-binding antigen 175 to erythrocytes. BAEBL (VSTK) does not bind to Gerbich-negative erythrocytes that express a truncated form of glycophorin C because it lacks exon 3. The N-linked oligosaccharide of Gerbich-negative glycophorin C has a markedly different composition than the wild-type glycophorin C. Moreover, removal of the Winked oligosaccharide from the wild-type glycophorin C eliminates its ability to inhibit binding of BAEBL (VSTK) to erythrocytes. These findings are consistent with the ligand for BAEBL (VSTK) being, in part, the N-linked oligosaccharide and suggest that single-point mutations in BAEBL allow A falciparum to recognize oligosaccharides on different erythrocyte surface glycoproteins or glycolipids, greatly increasing its invasion range.