Transferrin receptor 1 is a reticulocyte-specific receptor for Plasmodium vivax.

Transferrin receptor 1 is a reticulocyte-specific receptor for Plasmodium vivax.
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转铁蛋白受体1是用于疟原虫的网状细胞特异性受体。

DOI:
10.1126/science.aan1078
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发表时间:
2018-01-05
期刊:
Science (New York, N.Y.)
影响因子:
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通讯作者:
Tham WH
Tham WH
中科院分区:
其他
文献类型:
--
作者:
Gruszczyk J;Kanjee U;Chan LJ;Menant S;Malleret B;Lim NTY;Schmidt CQ;Mok YF;Lin KM;Pearson RD;Rangel G;Smith BJ;Call MJ;Weekes MP;Griffin MDW;Murphy JM;Abraham J;Sriprawat K;Menezes MJ;Ferreira MU;Russell B;Renia L;Duraisingh MT;Tham WH

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间日疟原虫对网织红细胞有严格的宿主嗜性。我们确定转铁蛋白受体1(TfR1)作为间日疟原虫网织红细胞结合蛋白2b(PvRBP2b)的受体。确定了参与红细胞结合的PvRBP2b的N-末端结构域的结构,阐明了TfR1识别的分子基础。通过TfR1表达敲低分析验证TfR1是PvRBP2b接合的生物靶标。PvRBP2b结合缺陷的TfR1突变体细胞对间日疟原虫的侵袭具有抗性,但对恶性疟原虫的侵袭没有抗性。使用巴西和泰国的临床分离株,我们表明抑制网织红细胞结合的PvRBP2b单克隆抗体也阻断间日疟原虫进入网织红细胞。这些数据表明,TfR1-PvRBP2b侵袭途径对于间日疟原虫侵袭期间网织红细胞的识别至关重要。
Plasmodium vivax shows a strict host tropism for reticulocytes. We identify transferrin receptor 1 (TfR1) as the receptor for P. vivax reticulocyte-binding protein 2b (PvRBP2b). The structure of the N-terminal domain of PvRBP2b involved in red blood cell binding was determined, elucidating the molecular basis for TfR1 recognition. TfR1 was validated as the biological target of PvRBP2b engagement by TfR1 expression knockdown analysis. TfR1 mutant cells deficient in PvRBP2b binding were refractory to invasion of P. vivax, but not to invasion of P. falciparum. Using Brazilian and Thai clinical isolates, we show that PvRBP2b monoclonal antibodies that inhibit reticulocyte binding also block P. vivax entry into reticulocytes. These data show that TfR1-PvRBP2b invasion pathway is critical for the recognition of reticulocytes during P. vivax invasion.
DOI: 10.1038/nature07327
发表时间: 2008-10-09
期刊: NATURE
影响因子: 64.8
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