The ubiquitin E3 ligase TRIM31 promotes aggregation and activation of the signaling adaptor MAVS through Lys63-linked polyubiquitination
The ubiquitin E3 ligase TRIM31 promotes aggregation and activation of the signaling adaptor MAVS through Lys63-linked polyubiquitination
复制标题
泛素 E3 连接酶 TRIM31 通过 Lys63 连接的多聚泛素化促进信号适配器 MAVS 的聚集和激活。
DOI：
10.1038/ni.3641
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发表时间：
2017-02-01
影响因子：
30.5
通讯作者：
Gao, Chengjiang
中科院分区：
文献类型：
--
作者：
Liu, Bingyu;Zhang, Meng;Gao, Chengjiang
信号转接子MAVS在病毒感染后形成类病毒聚集体，激活先天的抗病毒免疫反应。然而，调节MAV聚集的分子机制却知之甚少。在这里，我们发现TRIM31是TRIM蛋白家族的一种E3泛素连接酶，是MAV聚集的调节因子。TRIM31在病毒感染后被招募到线粒体，并通过RLR模式识别受体介导的抗病毒信号特异性调节。TRIM31基因缺陷的小鼠比野生型小鼠更容易感染RNA病毒。TRIM31与MAV相互作用并催化Lys63(K63)连接的Lys10、Lys311和Lys461在MAV上的多泛素化。这种修饰促进了病毒感染后小牛体内类病毒聚集体的形成。我们的发现揭示了通过TRIM31介导的K63连接的MAV泛素化来调节MAV聚集和细胞抗病毒反应的分子机制的新见解。
The signaling adaptor MAVS forms prion-like aggregates to activate an innate antiviral immune response after viral infection. However, the molecular mechanisms that regulate MAVS aggregation are poorly understood. Here we identified TRIM31, an E3 ubiquitin ligase of the TRIM family of proteins, as a regulator of MAVS aggregation. TRIM31 was recruited to mitochondria after viral infection and specifically regulated antiviral signaling mediated by RLR pattern-recognition receptors. TRIM31-deficient mice were more susceptible to infection with RNA virus than were wild-type mice. TRIM31 interacted with MAVS and catalyzed the Lys63 (K63)-linked polyubiquitination of Lys10, Lys311 and Lys461 on MAVS. This modification promoted the formation of prion-like aggregates of MAVS after viral infection. Our findings reveal new insights in the molecular regulation of MAVS aggregation and the cellular antiviral response through TRIM31-mediated K63-linked polyubiquitination of MAVS.