The Plasmodium falciparum family of rab GTPases
The Plasmodium falciparum family of rab GTPases
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DOI：
10.1016/s0378-1119(03)00381-0
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发表时间：
2003-03-13
期刊：
影响因子：
3.5
通讯作者：
Langsley, G
中科院分区：
文献类型：
--
作者：
Quevillon, E;Spielmann, T;Langsley, G
Rab gtpase是真核细胞囊泡运输的关键调节因子。在这里，我们寻求一个全球表征和描述的恶性疟原虫家族的Rab GTPases。我们结合了生物信息学分析、预测实验测试、结构建模和系统发育。这些分析鉴定出7种新的Rabs寄生虫。因此，我们估计恶性疟原虫家族由11个基因组成。我们发现这个家族的十个成员在感染的红细胞中被转录。关于这个家庭的各个成员，可以得出一系列具体的和全球性的结论。预测具有室特异性的Rabs显示不同的亚细胞分布。PfRab1A和PfRab11A通过产生特异性抗血清证实了这一点。序列分析揭示了几个特性，可能具有功能含义。其中一个转录基因Pfrab5b不编码经典的c端，这表明该GTPase具有新的调节作用。另一种是Pfrab5a，先前被鉴定为位于2号染色体上的兔基因，在其gtp结合区域有一个30个氨基酸的插入。结构方面的考虑表明，这种插入可能代表一种新的交互界面。我们使用保守的RabF和RabSF基序来区分特定的寄生虫Rabs，并遵循它们在PfRab6结构上的预测位置变化，因为GTP被水解成GDP。这使我们提出它们参与潜在的相互作用表面，我们将其扩展到人类Rab6和已知介导Rabkinesine-6结合的基序。最后，我们将恶性疟原虫rabb家族与酿酒酵母和pombe Schizosaccharomyces进行了比较，发现Rabs寄生虫可以分离成可能的功能分支。这样的分类可能会为Rab寄生虫的功能提供线索，并可能揭示恶性疟原虫的分泌/内吞途径。(C) 2003 Elsevier Science B.V.版权所有
Rab GTPases are key regulators of vesicular traffic in eukaryotic cells. Here we sought a global characterization and description of the Plasmodium falciparum family of Rab GTPases. We used a combination of bioinformatic analyses, experimental testing of predictions, structure modelling and phylogenetics. These analyses led to the identification of seven new parasite Rabs. Accordingly we estimate that the P. falciparum family is made up of 11 genes. We show that ten members of this family are transcribed in infected erythrocytes. Concerning the various members of the family, a series of specific as well as global conclusions can be drawn. Rabs predicted to be compartment-specific show different subcellular distributions. This is demonstrated for PfRab1A and PfRab11A, with the generation of specific antisera. The sequence analyses reveal several peculiarities, with possible functional implications. One of the transcribed genes, Pfrab5b, does not encode a classical C-terminus, suggestive of a novel regulatory role for this GTPase. Another, Pfrab5a, previously identified as a rab gene located on chromosome 2, possesses a 30-amino-acid insertion in its GTP-binding domain. Structural considerations suggest that this insertion could represent a novel interaction interface. We used conserved RabF and RabSF motifs to discriminate between specific parasite Rabs, and followed their predicted change in position on the structure of PfRab6, as GTP is hydrolysed to GDP. This allowed us to propose their involvement in potential interaction surfaces, that we extended to human Rab6 and the motifs known to mediate Rabkinesine-6 binding. Finally, we compared the P. falciparum Rab family to those of Saccharomyces cerevisiae and Schizosaccharomyces pombe and found that parasite Rabs segregate into possible functional clads. Such grouping into clads may give clues to parasite Rab function, and may shed light on P. falciparum secretory/endocytic pathways. (C) 2003 Elsevier Science B.V. All rights reserved.