A single, bi-functional aquaglyceroporin in blood-stage Plasmodium falciparum malaria parasites
A single, bi-functional aquaglyceroporin in blood-stage Plasmodium falciparum malaria parasites
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DOI：
10.1074/jbc.m110683200
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发表时间：
2002-02-15
影响因子：
4.8
通讯作者：
Beitz, E
中科院分区：
文献类型：
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作者：
Hansen, M;Kun, JFJ;Beitz, E
疟疾寄生虫恶性疟原虫在肾通道期间面临剧烈的渗透压变化，并在血液阶段的发育过程中参与甘油脂的大量生物合成。我们在即将完成的恶性疟原虫基因组中发现了一个与大肠杆菌甘油促进剂相似度最高的单一水甘油孔蛋白（PfAQP）（50.4％），但孔区域中的两个典型的Asn-Pro-Ala（NPA）基序分别变为Asn-Leu-Ala（NLA）和Asn-Pro-Ser（NPS）。在非洲爪蟾卵母细胞中的表达使其对水和甘油具有高度渗透性。最多五个碳的糖醇和尿素通过孔隙。 NLA/NPS 基序的突变分析显示了它们的结构重要性，但对称的孔特性得以保持。 PfAQP 在血液期寄生虫从环经滋养体到裂殖体的整个发育过程中表达，并且定位于寄生虫，但不定位于红细胞的细胞质或细胞膜。其独特的双功能表明其具有防止渗透压的功能，并有效地提供血清甘油库，用于 ATP 生成，主要用于磷脂合成。
The malaria parasite Plasmodium falciparum faces drastic osmotic changes during kidney passages and is engaged in the massive biosynthesis of glycerolipids during its development in the blood-stage. We identified a single aquaglyceroporin (PfAQP) in the nearly finished genome of P. falciparum with highest similarity to the Escherichia coli glycerol facilitator (50.4%), but both canonical Asn-Pro-Ala (NPA) motifs in the pore region are changed to Asn-Leu-Ala (NLA) and Asn-Pro-Ser (NPS), respectively. Expression in Xenopus oocytes renders them highly permeable for both water and glycerol. Sugar alcohols up to five carbons and urea pass the pore. Mutation analyses of the NLA/NPS motifs showed their structural importance, but the symmetrical pore properties were maintained. PfAQP is expressed in blood-stage parasites throughout the development from rings via trophozoites to schizonts and is localized to the parasite but not to the erythrocyte cytoplasm or membrane. Its unique bi-functionality indicates functions in the protection from osmotic stress and efficiently provides access to the serum glycerol pool for the use in ATP generation and primarily in the phospholipid synthesis.