Division of Molecular Medicine, Hefei National Laboratory for Physical Sciences at Microscale, CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences, University of Science and Technology of China, Hefei, 230027, China.
Adv Exp Med Biol. 2019;1172:157-188. doi: 10.1007/978-981-13-9367-9_8.
RIG-I-like receptors (RLRs) are an important family of pattern recognition receptors. They activate the immunological responses against viral infections by sensing RNAs in the cytoplasm. Recent studies provide significant insights into the activation and transduction mechanisms of RLRs family (members including RIG-I, MDA5, and LGP2). Here we review our current understanding of the structures of RLRs. Structural characterizations of RLRs family have revealed the mechanism of their actions at molecular level. The activation mechanisms of RIG-I and MDA5 are different, despite both of them have similar domain organizations and bind to dsRNA ligands. RIG-I, but not MDA5, adopts an auto-suppression conformation in the absence of RNA. In addition to ligand triggered receptor oligomerization, the activities of these receptors are also regulated by several posttranslational modifications, especially ubiquitination. Overall, these structural studies play critical roles in promoting the understanding of viral RNA recognition mechanisms by the host innate immune system, which also contribute to the designing of drugs for treatment of viral infection. However, much work remains to be done in studying the signaling pathway of MDA5 and LGP2, particularly by structural biology.
RLR 是模式识别受体（PRR）家族中的重要一员。它们通过识别细胞质中的 RNA 来激活针对病毒感染的免疫反应。最近的研究为 RLR 家族（包括 RIG-I、MDA5 和 LGP2 等成员）的激活和转导机制提供了重要的见解。在这里，我们综述了目前对 RLR 结构的认识。RLR 家族的结构特征揭示了它们在分子水平上的作用机制。尽管 RIG-I 和 MDA5 具有相似的结构域组织并结合 dsRNA 配体，但它们的激活机制却不同。在没有 RNA 的情况下，RIG-I 而不是 MDA5 采用自动抑制构象。除了配体触发的受体寡聚化外，这些受体的活性还受到几种翻译后修饰的调节，特别是泛素化。总的来说，这些结构研究对于促进宿主固有免疫系统对病毒 RNA 识别机制的理解起到了至关重要的作用，也为治疗病毒感染的药物设计做出了贡献。然而，在研究 MDA5 和 LGP2 的信号通路方面，还有许多工作要做，特别是通过结构生物学的方法。
