Structural analysis of RIG-I-like receptors reveals ancient rules of engagement between diverse RNA helicases and TRIM ubiquitin ligases.
Structural analysis of RIG-I-like receptors reveals ancient rules of engagement between diverse RNA helicases and TRIM ubiquitin ligases.
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DOI：
10.1016/j.molcel.2020.11.047
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发表时间：
2021-02-04
期刊：
影响因子：
16
通讯作者：
Hur S
中科院分区：
文献类型：
--
作者：
Kato K;Ahmad S;Zhu Z;Young JM;Mu X;Park S;Malik HS;Hur S
RNA解旋酶和E3泛素连接酶在细胞中介导许多关键功能，但它们的作用在很大程度上是在不同的生物学背景下研究的。在这里，我们发现进化保守的规则之间的RNA解旋酶和三方基序（TRIM）E3连接酶，导致其在脊椎动物先天免疫功能的协调。使用冷冻电子显微镜和生物化学，我们表明，RIG-I样受体（RLRs），病毒RNA受体与解旋酶结构域，通过类似的表位在解旋酶结构域与他们的同源TRIM/TRIM样E3连接酶相互作用。它们的相互作用是亲合力驱动的，限制了TRIM/TRIM样蛋白的作用和随后对RLR多聚体的免疫激活。质谱分析和生物学引导的生化分析进一步揭示了类似的参与规则可能适用于不同的RNA解旋酶和TRIM/TRIM样蛋白。我们的分析表明，不仅保守的底物TRIM蛋白，而且，出乎意料的是，深进化TRIM蛋白和RNA解旋酶之间的联系，连接泛素和RNA生物学在整个动物进化。适当的免疫功能需要多层制衡。Kato等显示了一种保守的机制，通过该机制，抗病毒蛋白RIG-1样受体与E3连接酶家族、TRIM样蛋白协作，以确保抗病毒免疫应答的高保真度和稳健性。
RNA helicases and E3 ubiquitin ligases mediate many critical functions in cells, but their actions have largely been studied in distinct biological contexts. Here, we uncover evolutionarily conserved rules of engagement between RNA helicases and tripartite motif (TRIM) E3 ligases that lead to their functional coordination in vertebrate innate immunity. Using cryoelectron microscopy and biochemistry, we show that RIG-I-like receptors (RLRs), viral RNA receptors with helicase domains, interact with their cognate TRIM/TRIM-like E3 ligases through similar epitopes in the helicase domains. Their interactions are avidity driven, restricting the actions of TRIM/TRIM-like proteins and consequent immune activation to RLR multimers. Mass spectrometry and phylogeny-guided biochemical analyses further reveal that similar rules of engagement may apply to diverse RNA helicases and TRIM/TRIM-like proteins. Our analyses suggest not only conserved substrates for TRIM proteins but also, unexpectedly, deep evolutionary connections between TRIM proteins and RNA helicases, linking ubiquitin and RNA biology throughout animal evolution. Proper immune function requires multiple layers of checks and balances. Kato et al. show a conserved mechanism by which the antiviral proteins RIG-I-like receptors collaborate with a family of E3 ligases, TRIM-like proteins, to ensure high fidelity and robustness of the antiviral immune response.
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影响因子：
64.8
作者：
Jiang, Fuguo;Ramanathan, Anand;Miller, Matthew T.;Tang, Guo-Qing;Gale, Michael, Jr.;Patel, Smita S.;Marcotrigiano, Joseph
通讯作者：
Marcotrigiano, Joseph
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影响因子：
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作者：
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通讯作者：
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影响因子：
64.8
作者：
Aguado LC;Schmid S;May J;Sabin LR;Panis M;Blanco-Melo D;Shim JV;Sachs D;Cherry S;Simon AE;Levraud JP;tenOever BR
通讯作者：
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影响因子：
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Bruns AM;Horvath CM
通讯作者：
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