Neutralization of toxic heme by Plasmodium falciparum histidine rich protein 2
Neutralization of toxic heme by Plasmodium falciparum histidine rich protein 2
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DOI：
10.1093/jb/mvg089
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发表时间：
2003-05-01
影响因子：
2.7
通讯作者：
Kamei, K
中科院分区：
文献类型：
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作者：
Huy, NT;Serada, S;Kamei, K
恶性疟原虫富含组氨酸的蛋白 2 (PfHRP2) 被认为是血红素聚合的引发剂（血红素是消化血红蛋白时的副产物），也是 H2O2 诱导的疟疾寄生虫食物液泡中血红素降解的促进剂。在这项工作中，我们设计了PfHRP2模型肽R18和R27（分别为18和27个残基），并将它们用于光学和电子自旋共振光谱测量，以确认血红素-PfHRP2复合物的轴向配体是源自PfHRP2组氨酸残基的咪唑部分的含氮供体。此外，我们发现R18和R27对血红素的亲和力分别为K-d = 2.21 x 10(-6) M和0.71 x 10(-6) M)可能与PfHRP2的亲和力一样高(K-d = 0.94 x 10(-6) M)。R27肽可以从膜插入的血红素中去除血红素并抑制血红素诱导的溶血。因此，我们提出PfHRP2的另一个功能：它可能通过从血红素结合膜中去除血红素或减少血红素诱导的溶血，在中和寄生虫细胞质和感染红细胞中的有毒血红素中发挥重要作用。
Plasmodium falciparum histidine-rich protein 2 (PfHRP2) has been suggested to be an initiator of the polymerization of heme, which is produced as by-product on the digestion of hemoglobin, and a promoter of the H2O2-induced degradation of heme in food vacuoles of the malarial parasite. In this work, we have designed PfHRP2 model peptides, R18 and R27 (18 and 27 residues, respectively), and used them for optical and electron spin resonance spectroscopic measurements to confirm that the axial ligands of the heme-PfHRP2 complex are the nitrogenous donors derived from the imidazole moieties of histidine residues of PfHRP2. In addition, we revealed that the affinities of R18 and R27 for heme K-d = 2.21 x 10(-6) M and 0.71 x 10(-6) M, respectively) might be as high as that of PfHRP2 (K-d = 0.94 x 10(-6) M) The R27 peptide can remove heme from membrane-intercalated heme and inhibit heme-induced hemolysis. Therefore, we suggest another function of PfHRP2: it may play an important role in the neutralization of toxic heme in the parasite cytoplasm and infected erythrocytes by removing heme from heme-bound membranes or reducing heme-induced hemolysis.