Plasmodium falciparum BAEBL Binds to Heparan Sulfate Proteoglycans on the Human Erythrocyte Surface
Plasmodium falciparum BAEBL Binds to Heparan Sulfate Proteoglycans on the Human Erythrocyte Surface
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DOI：
10.1074/jbc.m109.021576
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发表时间：
2010-01-15
影响因子：
4.8
通讯作者：
Akashi, Hiroomi
中科院分区：
文献类型：
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作者：
Kobayashi, Kyousuke;Kato, Kentaro;Akashi, Hiroomi
红细胞侵袭对于疟疾寄生虫恶性疟原虫的发病机制和生存至关重要。这一过程部分是由属于达菲结合样家族的蛋白质介导的，这些蛋白质在裂殖子表面表达。其中一种蛋白质 BAEBL（也称为 EBA-140）被认为以唾液酸依赖性方式与血型糖蛋白 C 结合。在本报告中，通过重组BAEBL蛋白与酶处理的红细胞之间的结合测定，我们表明BAEBL与红细胞的结合主要是通过唾液酸介导的，部分是通过硫酸乙酰肝素（HS）介导的。由于 BAEBL 与多种 HS 蛋白聚糖或纯化的 HS 结合，因此发现 BAEBL-HS 结合独立于 HS 蛋白聚糖肽主链和唾液酸部分的存在。此外，添加可溶性肝素会破坏唾液酸和 HS 依赖性结合。这种抑制可能是 BAEBL 与肝素结合的结果。侵袭分析表明，HS 依赖性结合与裂殖子侵袭效率相关。这些结果表明 HS 是促进 BAEBL 结合和裂殖子入侵的一个因素。此外，这些发现可以解释添加肝素和其他硫酸化糖复合物后观察到的侵袭抑制机制。
Erythrocyte invasion is critical to the pathogenesis and survival of the malarial parasite, Plasmodium falciparum. This process is partly mediated by proteins that belong to the Duffy binding-like family, which are expressed on the merozoite surface. One of these proteins, BAEBL (also known as EBA-140), is thought to bind to glycophorin C in a sialic acid-dependent manner. In this report, by the binding assay between recombinant BAEBL protein and enzyme-treated erythrocytes, we show that the binding of BAEBL to erythrocytes is mediated primarily by sialic acid and partially through heparan sulfate (HS). Because BAEBL binds to several kinds of HS proteoglycans or purified HS, the BAEBL-HS binding was found to be independent of the HS proteoglycan peptide backbone and the presence of sialic acid moieties. Furthermore, both the sialic acid-and HS-dependent binding were disrupted by the addition of soluble heparin. This inhibition may be the result of binding between BAEBL and heparin. Invasion assays demonstrated that HS-dependent binding was related to the efficiency of merozoite invasion. These results suggest that HS functions as a factor that promotes the binding of BAEBL and merozoite invasion. Moreover, these findings may explain the invasion inhibition mechanisms observed following the addition of heparin and other sulfated glycoconjugates.