Background

Histone deacetylase 8 from Schistosoma mansoni (SmHDAC8) is essential to parasite growth and development within the mammalian host and is under investigation as a target for the development of selective inhibitors as novel schistosomicidal drugs. Although some protein substrates and protein partners of human HDAC8 have been characterized, notably indicating a role in the function of the cohesin complex, nothing is known of the partners and biological function of SmHDAC8.

Methodology/Principal findings

We therefore employed two strategies to characterize the SmHDAC8 interactome. We first used SmHDAC8 as a bait protein in yeast two-hybrid (Y2H) screening of an S. mansoni cDNA library. This allowed the identification of 49 different sequences encoding proteins. We next performed co-immunoprecipitation (Co-IP) experiments on parasite extracts with an anti-SmHDAC8 antibody. Mass spectrometry (MS) analysis allowed the identification of 160 different proteins.

Conclusions/Significance

SmHDAC8 partners are involved in about 40 different processes, included expected functions such as the cohesin complex, cytoskeleton organization, transcriptional and translational regulation, metabolism, DNA repair, the cell cycle, protein dephosphorylation, proteolysis, protein transport, but also some proteasome and ribosome components were detected. Our results show that SmHDAC8 is a versatile deacetylase, potentially involved in both cytosolic and nuclear processes.

中文翻译：

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曼氏血吸虫组蛋白脱乙酰基酶8的相互作用组分析

背景

来自曼氏血吸虫的组蛋白脱乙酰基酶8 （Sm HDAC8）对哺乳动物宿主体内的寄生虫生长和发育至关重要，并且正在作为选择性抑制剂作为新型血吸虫杀伤剂的开发目标进行研究。尽管已鉴定了人类HDAC8的某些蛋白质底物和蛋白质伴侣，特别是表明它们在粘着蛋白复合物功能中的作用，但对Sm HDAC8的伴侣和生物学功能一无所知。

方法/主要发现

因此，我们采用了两种策略来表征Sm HDAC8相互作用组。我们首先将Sm HDAC8用作诱饵蛋白，用于酵母S的双杂交（Y2H）筛选。mansoni cDNA文库。这样就可以鉴定出49种编码蛋白质的不同序列。接下来，我们用抗Sm HDAC8抗体对寄生虫提取物进行了共免疫沉淀（Co-IP）实验。质谱（MS）分析可以鉴定160种不同的蛋白质。

结论/意义

Sm HDAC8伙伴参与了大约40个不同的过程，包括预期功能，例如粘着蛋白复合物，细胞骨架组织，转录和翻译调节，代谢，DNA修复，细胞周期，蛋白质去磷酸化，蛋白水解，蛋白质转运，还包括一些蛋白酶体和检测到核糖体成分。我们的结果表明，Sm HDAC8是一种多功能的脱乙酰基酶，可能参与胞质和核过程。