Lampitella Erosantonio, Landi Nicola, Oliva Rosario, Gaglione Rosa, Bosso Andrea, De Lise Federica, Ragucci Sara, Arciello Angela, Petraccone Luigi, Pizzo Elio, Del Vecchio Pompea, Di Maro Antimo
Department of Chemical Sciences, University of Naples 'Federico II', Via Cintia, 80126 Napoli, Italy.
Department of Environmental, Biological and Pharmaceutical Sciences and Technologies (DiSTABiF), University of Campania 'Luigi Vanvitelli', Via Vivaldi 43, 81100 Caserta, Italy.
J Biochem. 2021 Dec 4;170(4):473-482. doi: 10.1093/jb/mvab062.
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.
老化菌素是一种新的类核糖体毒素蛋白家族的原型，最近在担子菌中也被发现。该蛋白通过切割位于大核糖体RNA的肌动蛋白/蓖麻毒素环处的单个磷酸二酯键表现出特异性核糖核酸酶活性，从而在早期阶段抑制蛋白质生物合成。与其他核糖体毒素相反，其活性需要二价阳离子的存在。在本研究中，我们报告了老化菌素对原核细胞和真核细胞的活性，表明该蛋白对癌细胞活力有显著影响，而对真核细胞和细菌细胞没有影响。为了合理解释这些发现，我们探索了该蛋白与模拟正常、癌症和细菌细胞膜的各种脂质体相互作用的能力。收集到的结果表明，老化菌素可以与用作癌细胞膜模型的二棕榈酰磷脂酰胆碱/二棕榈酰磷脂酰丝氨酸/胆固醇囊泡以及用作细菌细胞膜模型的二棕榈酰磷脂酰胆碱/二棕榈酰磷脂酰甘油囊泡相互作用，这表明它与阴离子脂质存在选择性相互作用。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，这可能是老化菌素对癌细胞具有选择性毒性的基础。
