New role of gramicidin A in RIG-I-like receptors-mediated IFN signalling

文献类型： 外文期刊

第一作者： Li, Xiao

作者： Li, Xiao;Sun, Xinyuan;Pang, Zhaojun;Yang, Han;Ji, Xiaoxin;Lei, Yi;Mu, Xin;Li, Xiao;Sun, Xinyuan;Pang, Zhaojun;Yang, Han;Ji, Xiaoxin;Lei, Yi;Mu, Xin;Yan, Zhongyi;Guo, Xiangqian;Zhao, Zhenxiang;Zhu, Zixiang;Zhu, Zixiang;Guo, Xiangqian;Mu, Xin;Mu, Xin

作者机构：

关键词： GOF; gramicidin A; IFN; MAVS; MDA5; RIG-I

期刊名称：IMMUNOLOGY （ 影响因子：6.4； 五年影响因子：7.0 ）

ISSN： 0019-2805

年卷期： 2023 年 169 卷 2 期

页码：

收录情况： SCI

摘要： The pattern recognition receptors (PRRs) sense exogenous molecular patterns most commonly derived from invading pathogens, to active the interferon (IFN) signalling. In the cytoplasm, the viral double-stranded RNAs (dsRNAs) are sensed by retinoic acid-inducible gene I (RIG-I) or melanoma differentiation-associated protein 5 (MDA5), depending on the length and chemical properties. Through the binding and oligomerizing onto the RNAs, they form filament to initiate the signalling cascade. Regulation of these receptors' activities are essential for manipulating the strength of IFN signalling. Here, through the virtual screening of chemical reagents using the published MDA5-dsRNA complex structure (PDB: 4GL2), we identified an antibiotic, gramicidin A as a stimulator that enhanced MDA5-mediated IFN signalling. Cytotoxic assay and IFN signalling assay suggested that disruption of lipid membrane, which is a well-defined mechanism of gramicidin A to perform its action, was dispensable in this process. Sucrose gradient ultracentrifugation assay showed that the gramicidin A treatment enhanced MDA5 oligomerization status in the presence of dsRNA. Our work implicated a new role of gramicidin A in innate immunity and presented a new tool to manipulate MDA5 activity.

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