D'Anna Luisa, Froux Aurane, Rainot Aurianne, Spinello Angelo, Perricone Ugo, Barbault Florent, Grandemange Stéphanie, Barone Giampaolo, Terenzi Alessio, Monari Antonio
Department of Biological, Chemical and Pharmaceutical Sciences and Technologies, Università di Palermo, Viale delle Scienze, Edificio 17, Palermo, 90128, Italy.
Université de Lorraine and CNRS, UMR 7039 CRAN, Nancy, F-54000, France.
Chemistry. 2024 Dec 18;30(71):e202403572. doi: 10.1002/chem.202403572. Epub 2024 Nov 6.
The presence of a guanine quadruplex in the opening reading frame of the messenger RNA coding for the transmembrane serine protease 2 (TMPRSS2) may pave the way to original anticancer and host-oriented antiviral strategy. Indeed, TMPRSS2 in addition to being overexpressed in different cancer types, is also related to the infection of respiratory viruses, including SARS-CoV-2, by promoting the cellular and viral membrane fusion through its proteolytic activity. The design of selective ligands targeting TMPRSS2 messenger RNA requires a detailed knowledge, at atomic level, of its structure. Therefore, we have used an original experimental-computational protocol to predict the first resolved structure of the parallel guanine quadruplex secondary structure in the RNA of TMPRSS2, which shows a rigid core flanked by a flexible loop. This represents the first atomic scale structure of the guanine quadruplex structure present in TMPRSS2 messenger RNA.
在编码跨膜丝氨酸蛋白酶2（TMPRSS2）的信使核糖核酸的开放阅读框中存在鸟嘌呤四链体，这可能为创新的抗癌和宿主导向抗病毒策略铺平道路。事实上，TMPRSS2除了在不同癌症类型中过度表达外，还通过其蛋白水解活性促进细胞和病毒膜融合，与包括严重急性呼吸综合征冠状病毒2（SARS-CoV-2）在内的呼吸道病毒感染有关。设计靶向TMPRSS2信使核糖核酸的选择性配体需要在原子水平上详细了解其结构。因此，我们使用了一种独创的实验-计算方案来预测TMPRSS2核糖核酸中平行鸟嘌呤四链体二级结构的首个解析结构，该结构显示出一个由柔性环侧翼的刚性核心。这代表了TMPRSS2信使核糖核酸中存在的鸟嘌呤四链体结构的首个原子尺度结构。
