Proteome-wide analysis reveals widespread lysine acetylation of major protein complexes in the malaria parasite.
Proteome-wide analysis reveals widespread lysine acetylation of major protein complexes in the malaria parasite.
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DOI：
10.1038/srep19722
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发表时间：
2016-01-27
影响因子：
4.6
通讯作者：
Llinás M
中科院分区：
文献类型：
--
作者：
Cobbold SA;Santos JM;Ochoa A;Perlman DH;Llinás M
赖氨酸乙酰化是包括恶性疟原虫在内的许多生物体中普遍存在的一种翻译后修饰，但整个寄生虫蛋白质组的乙酰化程度仍未解决。此外，乙酰化的功能意义或特定的乙酰赖氨酸位点是如何调节的在很大程度上是未知的。在这里，我们报道了已知寄生虫‘乙酰体’的7倍扩大，表征了1,146个蛋白质上的2,876个乙酰化位点。我们观察到，赖氨酸乙酰化靶向一系列不同的蛋白质复合体，尤其是在Apicomplexan AP2(ApiAP2)DNA结合蛋白家族中。利用定量蛋白质组学方法，我们确定了对醋酸酯/乙酰辅酶A平衡的人为干扰改变了几个ApiAP2 DNA结合蛋白和相关转录蛋白的乙酰赖氨酸占有率。这种代谢信号可以介导显著的下游转录反应，因为我们表明，ApiAP2DNA结合域的乙酰化消除了其与DNA结合的倾向。最后，我们研究了每一类赖氨酸脱乙酰酶的乙酰赖氨酸靶标，以开始探索每一类酶对恶性疟原虫乙酸组的调节作用。
Lysine acetylation is a ubiquitous post-translational modification in many organisms including the malaria parasite Plasmodium falciparum, yet the full extent of acetylation across the parasite proteome remains unresolved. Moreover, the functional significance of acetylation or how specific acetyl-lysine sites are regulated is largely unknown. Here we report a seven-fold expansion of the known parasite ‘acetylome’, characterizing 2,876 acetylation sites on 1,146 proteins. We observe that lysine acetylation targets a diverse range of protein complexes and is particularly enriched within the Apicomplexan AP2 (ApiAP2) DNA-binding protein family. Using quantitative proteomics we determined that artificial perturbation of the acetate/acetyl-CoA balance alters the acetyl-lysine occupancy of several ApiAP2 DNA-binding proteins and related transcriptional proteins. This metabolic signaling could mediate significant downstream transcriptional responses, as we show that acetylation of an ApiAP2 DNA-binding domain ablates its DNA-binding propensity. Lastly, we investigated the acetyl-lysine targets of each class of lysine deacetylase in order to begin to explore how each class of enzyme contributes to regulating the P. falciparum acetylome.