A novel tetratricopeptide repeat (TPR) containing PP5 serine/threonine protein phosphatase in the malaria parasite, Plasmodium falciparum.
A novel tetratricopeptide repeat (TPR) containing PP5 serine/threonine protein phosphatase in the malaria parasite, Plasmodium falciparum.
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DOI：
10.1186/1471-2180-1-31
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发表时间：
2001
期刊：
影响因子：
4.2
通讯作者：
Barik S
中科院分区：
文献类型：
--
作者：
Dobson S;Kar B;Kumar R;Adams B;Barik S
疟疾寄生虫恶性疟原虫(PF)在全球造成近200万人死亡。然而，寄生虫中的细胞信号机制在很大程度上仍不清楚。最近发现的一些蛋白激酶和磷酸酶表明，寄生虫中存在一个蓬勃发展的可逆磷酸化系统，尽管它们的功能和调节还需要确定。我们提供了恶性疟原虫中一种蛋白丝氨酸/苏氨酸磷酸酶PP5的生化和序列证据，并将其命名为PfPP5。该594个氨基酸的多肽由寄生虫的1785个核苷酸长的无内含子基因编码。在细菌中表达的重组蛋白与天然的PfPP5没有什么区别。测序比较表明，PfPP5在催化核心外的超长N末端含有四个四肽重复序列(TPR)，而在其他PP5磷酸酶中有三个这样的重复序列。PfPP5的N末端是多不饱和脂肪酸刺激磷酸酶活性所必需的。免疫共沉淀证实了天然PfPP5与PF热休克蛋白90(HSP90)之间的相互作用。PfPP5在所有无性红细胞期均有表达，对冈田酸中度敏感。这是寄生虫Apicomplexa家族中第一个TPR结构域蛋白的例子。由于TPR结构域在蛋白质相互作用中发挥着重要作用，特别是与PP5磷酸酶的调节有关，因此PfPP5注定在寄生生长和信号通路中具有决定性的作用。PfPP5和同源伴侣HSP90之间的相互作用就是例证。
The malarial parasite, Plasmodium falciparum (Pf), is responsible for nearly 2 million deaths worldwide. However, the mechanisms of cellular signaling in the parasite remain largely unknown. Recent discovery of a few protein kinases and phosphatases point to a thriving reversible phosphorylation system in the parasite, although their function and regulation need to be determined. We provide biochemical and sequence evidence for a protein serine/threonine phosphatase type PP5 in Plasmodium falciparum, and named it PfPP5. The 594-amino acid polypeptide was encoded by a 1785 nucleotide long intronless gene in the parasite. The recombinant protein, expressed in bacteria, was indistinguishable from native PfPP5. Sequencing comparison indicated that the extra-long N-terminus of PfPP5 outside the catalytic core contained four tetratricopeptide repeats (TPRs), compared to three such repeats in other PP5 phosphatases. The PfPP5 N-terminus was required for stimulation of the phosphatase activity by polyunsaturated fatty acids. Co-immunoprecipitation demonstrated an interaction between native PfPP5 and Pf heat shock protein 90 (hsp90). PfPP5 was expressed in all the asexual erythrocytic stages of the parasite, and was moderately sensitive to okadaic acid. This is the first example of a TPR-domain protein in the Apicomplexa family of parasites. Since TPR domains play important roles in protein-protein interaction, especially relevant to the regulation of PP5 phosphatases, PfPP5 is destined to have a definitive role in parasitic growth and signaling pathways. This is exemplified by the interaction between PfPP5 and the cognate chaperone hsp90.