Gruszczyk Jakub, Kanjee Usheer, Chan Li-Jin, Menant Sébastien, Malleret Benoit, Lim Nicholas T Y, Schmidt Christoph Q, Mok Yee-Foong, Lin Kai-Min, Pearson Richard D, Rangel Gabriel, Smith Brian J, Call Melissa J, Weekes Michael P, Griffin Michael D W, Murphy James M, Abraham Jonathan, Sriprawat Kanlaya, Menezes Maria J, Ferreira Marcelo U, Russell Bruce, Renia Laurent, Duraisingh Manoj T, Tham Wai-Hong
The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia.
Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, Boston, MA 02115, USA.
Science. 2018 Jan 5;359(6371):48-55. doi: 10.1126/science.aan1078.
shows a strict host tropism for reticulocytes. We identified transferrin receptor 1 (TfR1) as the receptor for reticulocyte-binding protein 2b (PvRBP2b). We determined the structure of the N-terminal domain of PvRBP2b involved in red blood cell binding, elucidating the molecular basis for TfR1 recognition. We validated TfR1 as the biological target of PvRBP2b engagement by means of TfR1 expression knockdown analysis. TfR1 mutant cells deficient in PvRBP2b binding were refractory to invasion of but not to invasion of Using Brazilian and Thai clinical isolates, we show that PvRBP2b monoclonal antibodies that inhibit reticulocyte binding also block entry into reticulocytes. These data show that TfR1-PvRBP2b invasion pathway is critical for the recognition of reticulocytes during invasion.
显示出对网织红细胞有严格的宿主嗜性。我们鉴定出转铁蛋白受体1（TfR1）是网织红细胞结合蛋白2b（PvRBP2b）的受体。我们确定了参与红细胞结合的PvRBP2b N末端结构域的结构，阐明了TfR1识别的分子基础。我们通过TfR1表达敲低分析验证了TfR1是PvRBP2b结合的生物学靶点。缺乏PvRBP2b结合的TfR1突变细胞对[疟原虫名称1]的入侵具有抗性，但对[疟原虫名称2]的入侵不具有抗性。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单克隆抗体也能阻断[疟原虫名称]进入网织红细胞。这些数据表明，TfR1 - PvRBP2b入侵途径对于[疟原虫名称]入侵期间网织红细胞的识别至关重要。 （注：原文中[疟原虫名称1]、[疟原虫名称2]、[疟原虫名称]处原文未明确写出具体名称，翻译时保留原样）
