The E3 ligase Riplet promotes RIG-I signaling independent of RIG-I oligomerization.
The E3 ligase Riplet promotes RIG-I signaling independent of RIG-I oligomerization.
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DOI：
10.1038/s41467-023-42982-0
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发表时间：
2023-11-11
影响因子：
16.6
通讯作者：
Pyle, Anna Marie
中科院分区：
文献类型：
--
作者：
Wang, Wenshuai;Goette, Benjamin;Guo, Rong;Pyle, Anna Marie
RIG-I是一种对RNA病毒感染有反应的必需先天免疫受体。RIG-I信号级联由一系列翻译后修饰介导，其中最重要的是E3连接酶Riplet对RIG-I半胱天冬酶募集结构域（CARD）的泛素化。这是RIG-I与其下游衔接蛋白MAVS之间相互作用所必需的，但作用机制仍不清楚。在这里，我们表明，Riplet是所需的RIG-I信号在短和长的dsRNA的存在下，建立Riplet激活不依赖于长的dsRNA上的RIG-I丝的形成。同样，定量Riplet-RIG-I亲和力测量确定Riplet与RIG-I相互作用，而不管受体是否与RNA结合。为了理解这一点，我们解决了RIG-I/RNA/Riplet复合物的高分辨率cryo-EM结构，揭示了控制Riplet介导的激活的分子界面，并能够为Riplet在信号传导中的作用制定统一的模型。Riplet将K63-Ub链缀合至RIG-I以诱导稳健的抗病毒应答，但作用机制仍不清楚。在这里，作者表明Riplet识别RIG-I，而不管其RNA结合状态如何，并促进RIG-I信号传导，而不依赖于RIG-I寡聚化。
RIG-I is an essential innate immune receptor that responds to infection by RNA viruses. The RIG-I signaling cascade is mediated by a series of post-translational modifications, the most important of which is ubiquitination of the RIG-I Caspase Recruitment Domains (CARDs) by E3 ligase Riplet. This is required for interaction between RIG-I and its downstream adapter protein MAVS, but the mechanism of action remains unclear. Here we show that Riplet is required for RIG-I signaling in the presence of both short and long dsRNAs, establishing that Riplet activation does not depend upon RIG-I filament formation on long dsRNAs. Likewise, quantitative Riplet-RIG-I affinity measurements establish that Riplet interacts with RIG-I regardless of whether the receptor is bound to RNA. To understand this, we solved high-resolution cryo-EM structures of RIG-I/RNA/Riplet complexes, revealing molecular interfaces that control Riplet-mediated activation and enabling the formulation of a unified model for the role of Riplet in signaling. Riplet conjugates K63-Ub chain to RIG-I in order to induce a robust antiviral response, but the mechanism of action remains unclear. Here, the authors show that Riplet recognizes RIG-I regardless of its RNA-bound status and promotes RIG-I signaling independent of RIG-I oligomerization.
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影响因子：
4.4
作者：
Burkart, Sandy S.;Schweinoch, Darius;Frankish, Jamie;Sparn, Carola;Wuest, Sandra;Urban, Christian;Merlo, Marta;Magalhaes, Vladimir G.;Piras, Antonio;Pichlmair, Andreas;Willemsen, Joschka;Kaderali, Lars;Binder, Marco
通讯作者：
Binder, Marco
影响因子：
39.3
作者：
Li D;Wu M
通讯作者：
Wu M
DOI：
10.1107/s2059798318009324
发表时间：
2018-09-01
期刊：
Acta crystallographica. Section D, Structural biology
影响因子：
--
作者：
Afonine PV;Klaholz BP;Moriarty NW;Poon BK;Sobolev OV;Terwilliger TC;Adams PD;Urzhumtsev A
通讯作者：
Urzhumtsev A
影响因子：
16
作者：
Kato K;Ahmad S;Zhu Z;Young JM;Mu X;Park S;Malik HS;Hur S
通讯作者：
Hur S
影响因子：
64.8
作者：
Peisley A;Wu B;Xu H;Chen ZJ;Hur S
通讯作者：
Hur S