LGP2 synergy with MDA5 in RLR-mediated RNA recognition and antiviral signaling.
LGP2 synergy with MDA5 in RLR-mediated RNA recognition and antiviral signaling.
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DOI：
10.1016/j.cyto.2015.02.010
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发表时间：
2015-08
期刊：
影响因子：
3.8
通讯作者：
Horvath CM
中科院分区：
文献类型：
--
作者：
Bruns AM;Horvath CM
哺乳动物细胞具有识别病毒感染并产生强大抗病毒反应的能力。模式识别受体蛋白检测病毒感染的分子特征并激活抗病毒信号。rig - i样受体（RLR）蛋白在几乎所有细胞的细胞质中表达，并特异性识别病毒衍生的RNA物种，作为区分病原体和宿主的分子特征。RLR家族由三个同源蛋白rig - 1、MDA5和LGP2组成。所有rlr都具有检测病毒衍生的dsRNA和水解ATP的能力，但在酶活性、内在识别RNA的能力和激活机制方面表现出个体差异。新出现的证据表明MDA5和rig - 1利用不同的机制沿着dsRNA形成寡聚物复合物。它们的信号域对齐创建了一个能够传播和放大抗病毒信号反应的平台。完整ATP水解的LGP2对于mda5介导的抗病毒应答至关重要，但LGP2缺乏激活抗病毒信号所必需的结构域，这使得LGP2在抗病毒信号传导中的作用尚不清楚。最近的研究揭示了LGP2和MDA5协同作用导致抗病毒信号增强的机制基础。本文简要总结了RLR系统，重点介绍了LGP2和MDA5之间的关系，详细描述了这两种蛋白如何共同检测外源RNA并产生全功能抗病毒应答。
Mammalian cells have the ability to recognize virus infection and mount a powerful antiviral response. Pattern recognition receptor proteins detect molecular signatures of virus infection and activate antiviral signaling. The RIG-I-like receptor (RLR) proteins are expressed in the cytoplasm of nearly all cells and specifically recognize virus-derived RNA species as a molecular feature discriminating the pathogen from the host. The RLR family is composed of three homologous proteins, RIG-I, MDA5, and LGP2. All RLRs have the ability to detect virus-derived dsRNA and hydrolyze ATP, but display individual differences in enzymatic activity, intrinsic ability to recognize RNA, and mechanisms of activation. Emerging evidence suggests that MDA5 and RIG-I utilize distinct mechanisms to form oligomeric complexes along dsRNA. Aligning of their signaling domains creates a platform capable of propagating and amplifying antiviral signaling responses. LGP2 with intact ATP hydrolysis is critical for the MDA5-mediated antiviral response, but LGP2 lacks the domains essential for activation of antiviral signaling, leaving the role of LGP2 in antiviral signaling unclear. Recent studies revealed a mechanistic basis of synergy between LGP2 and MDA5 leading to enhanced antiviral signaling. This review briefly summarizes the RLR system, and focuses on the relationship between LGP2 and MDA5, describing in detail how these two proteins work together to detect foreign RNA and generate a fully functional antiviral response.
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影响因子：
64.8
作者：
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影响因子：
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