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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Characterization of a UBC13 kinase in Plasmodium falciparum
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Characterization of a UBC13 kinase in Plasmodium falciparum

机译：恶性疟原虫中UBC13激酶的表征

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摘要

Protein kinases are generally recognized as attractive drug targets to treat a variety of human diseases. Recent analysis of the Plasmodium falciparum kinome identified several kinases that are entirely unique to Plasmodium species. The specific functions and targets of most of these enzymes remain largely unknown. Here, we have identified a P. falciparum kinase (PfPK9/PF13_0085 ORF) that does not cluster with any of the typical eukaryotic protein kinases. PfPK9 protein expression was induced ≈ 18 h after red blood cell infection, and was mainly localized to the parasitophorous vacuolar membrane as well as the cytosol. Recombinant PfPK9 autophosphorylated in vitro and specifically phosphorylated the exogenous substrate histone H1, indicating that it is catalytically active. Phosphopeptide mapping studies showed that autophosphorylation occurred at three residues: T082, T265, and T269. We identified a P. falciparum homolog of the E2 ubiquitin-conjugating enzyme 13 (UBC13) as an endogenous substrate for PfPK9. PfPK9 phosphorylated UBC13 at S106, a highly conserved residue among eukaryotic E2s, and suppressed its ubiquitin-conjugating activity. Our findings not only describe a previously uncharacterized Plasmodium kinase and its likely in vivo target, but also suggest that modulation of UBC13 activity by phosphorylation may be a common regulatory mechanism in eukaryotes.
机译：蛋白激酶通常被认为是治疗多种人类疾病的有吸引力的药物靶标。最近对恶性疟原虫激酶基因组的分析发现了几种疟原虫物种完全独特的激酶。大多数这些酶的特异性功能和靶标在很大程度上仍然未知。在这里，我们确定了恶性疟原虫激酶（PfPK9 / PF13_0085 ORF），它与任何典型的真核蛋白激酶均不聚集。 PfPK9蛋白表达在红细胞感染后约18小时被诱导，并且主要定位在寄生虫的液泡膜以及细胞质中。重组PfPK9在体外自磷酸化，特别是外源底物组蛋白H1磷酸化，表明它具有催化活性。磷酸肽图研究显示自磷酸化发生在三个残基：T082，T265和T269。我们确定了E2泛素结合酶13（UBC13）的恶性疟原虫同源物是PfPK9的内源性底物。 PfPK9在S106处使UBC13磷酸化，UBC13是真核E2中高度保守的残基，并抑制了其泛素结合活性。我们的发现不仅描述了以前未知的疟原虫激酶及其可能的体内靶标，而且还表明通过磷酸化调节UBC13活性可能是真核生物中常见的调控机制。

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