Ageritin is the prototype of a new ribotoxin-like protein family, which has been recently identified also in basidiomycetes. The protein exhibits specific RNase activity through the cleavage of a single phosphodiester bond located at sarcin/ricin loop of the large rRNA, thus inhibiting protein biosynthesis at early stages. Conversely to other ribotoxins, its activity requires the presence of divalent cations. In the present study, we report the activity of Ageritin on both prokaryotic and eukaryotic cells showing that the protein has a prominent effect on cancer cells viability and no effects on eukaryotic and bacterial cells. In order to rationalize these findings, the ability of the protein to interact with various liposomes mimicking normal, cancer and bacterial cell membranes was explored. The collected results indicate that Ageritin can interact with DPPC/DPPS/Chol vesicles, used as a model of cancer cell membranes, and with DPPC/DPPG vesicles, used as a model of bacterial cell membranes, suggesting a selective interaction with anionic lipids. However, a different perturbation of the two model membranes, mediated by cholesterol redistribution, was observed and this might be at the basis of Ageritin selective toxicity towards cancer cells.

中文翻译：

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核毒素样蛋白Ageritin的毒性和膜扰动特性

Ageritin 是一种新的核毒素样蛋白家族的原型，最近在担子菌中也发现了这种蛋白家族。该蛋白质通过裂解位于大 rRNA 的 sarcin/ricin 环上的单个磷酸二酯键表现出特定的 RNase 活性，从而在早期阶段抑制蛋白质的生物合成。与其他核毒素相反，它的活性需要存在二价阳离子。在本研究中，我们报告了 Ageritin 对原核和真核细胞的活性，表明该蛋白对癌细胞活力有显着影响，而对真核细胞和细菌细胞没有影响。为了使这些发现合理化，研究了蛋白质与模拟正常、癌症和细菌细胞膜的各种脂质体相互作用的能力。收集的结果表明，Ageritin 可以与用作癌细胞膜模型的 DPPC/DPPS/Chol 囊泡相互作用，并与用作细菌细胞膜模型的 DPPC/DPPG 囊泡相互作用，表明与阴离子脂质有选择性相互作用。然而，观察到由胆固醇重新分布介导的两种模型膜的不同扰动，这可能是 Ageritin 对癌细胞的选择性毒性的基础。