疟疾寄生虫clag3基因决定受感染的红细胞通过道介导吸收营养
Wang Nguitragool1, Abdullah A B Bokhari, Ajay D Pillai
1The Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA.
Cell
|May 31, 2011
概括
研究人员确定了等离子体表面离子通道 (PSAC) 的分子基础,这是疟疾寄生虫中关键的营养物质载体. 这一发现揭示了抗疟疾药物开发的新目标.
科学领域:
- 寄生虫学的寄生虫学
- 分子生物学分子生物学
- 药物发现 药物发现 药物发现
背景情况:
- 红细胞中疟疾寄生虫的发展需要通过宿主细胞膜吸收营养.
- 等离子体表面离子通道 (PSAC) 便于这种传输,是经过验证的抗疟疾点.
- 然而,PSAC的精确分子身份和功能仍然难以捉摸.
研究的目的:
- 为了确定负责PSAC活动的寄生虫基因.
- 为了阐明在Plasmodium falciparum中通过红细胞膜运输营养的分子基础.
- 通过描述其抑制剂相互作用来验证PSAC作为药物标.
主要方法:
- 对营养吸收抑制剂进行高通量选.
- 使用P. falciparum交叉 (Dd2 × HB3) 的遗传映射.
- DNA转染和体外选择实验.
- 对clag3基因表达和蛋白质定位的分析.
主要成果:
- 确定了一种高度针对P. falciparum PSAC的特异性化合物.
- PSAC活动被映射到染色体3上的单个位置,对应于两个clag3基因.
- 这些clag3基因编码了一种介导溶液透性的整体膜蛋白.
- 观察到clag3基因的表达切换.
结论:
- 克拉格3基因家族编码了等离子体表面离子通道 (PSAC).
- 在疟疾寄生虫内红细胞发育过程中,PSAC对于营养吸收至关重要.
- 这种clag3编码的蛋白质代表了抗疟疾药物开发的有希望的新目标.
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