Jiang Qiu-Xing
Department of Microbiology and Cell Science, University of Florida, Gainesville, FL 32611, United States.
Med Chem. 2019;15(5):443-458. doi: 10.2174/1573406415666181219101613.
Cells need high-sensitivity detection of non-self molecules in order to fight against pathogens. These cellular sensors are thus of significant importance to medicinal purposes, especially for treating novel emerging pathogens. RIG-I-like receptors (RLRs) are intracellular sensors for viral RNAs (vRNAs). Their active forms activate mitochondrial antiviral signaling protein (MAVS) and trigger downstream immune responses against viral infection. Functional and structural studies of the RLR-MAVS signaling pathway have revealed significant supramolecular variability in the past few years, which revealed different aspects of the functional signaling pathway. Here I will discuss the molecular events of RLR-MAVS pathway from the angle of detecting single copy or a very low copy number of vRNAs in the presence of non-specific competition from cytosolic RNAs, and review key structural variability in the RLR / vRNA complexes, the MAVS helical polymers, and the adapter-mediated interactions between the active RLR / vRNA complex and the inactive MAVS in triggering the initiation of the MAVS filaments. These structural variations may not be exclusive to each other, but instead may reflect the adaptation of the signaling pathways to different conditions or reach different levels of sensitivity in its response to exogenous vRNAs.
细胞需要对非自身分子进行高灵敏度检测，以便对抗病原体。因此，这些细胞传感器对于医学目的具有重要意义，特别是在治疗新型病原体方面。视黄酸诱导基因I样受体（RLR）是病毒RNA（vRNA）的细胞内传感器。它们的活性形式激活线粒体抗病毒信号蛋白（MAVS），并触发针对病毒感染的下游免疫反应。在过去几年中，RLR-MAVS信号通路的功能和结构研究揭示了显著的超分子变异性，这揭示了功能信号通路的不同方面。在这里，我将从在存在来自细胞质RNA的非特异性竞争的情况下检测单拷贝或极低拷贝数的vRNA的角度讨论RLR-MAVS通路的分子事件，并回顾RLR/vRNA复合物、MAVS螺旋聚合物以及活性RLR/vRNA复合物与无活性MAVS之间的衔接子介导的相互作用在触发MAVS丝起始过程中的关键结构变异性。这些结构变异可能并非相互排斥，而是可能反映了信号通路对不同条件的适应性，或者在对外源vRNA的反应中达到不同水平的敏感性。
