The Antiviral Enzyme, Viperin, Activates Protein Ubiquitination by the E3 Ubiquitin Ligase, TRAF6,Journal of the American Chemical Society

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The Antiviral Enzyme, Viperin, Activates Protein Ubiquitination by the E3 Ubiquitin Ligase, TRAF6
Journal of the American Chemical Society ( IF 14.4 ) Pub Date : 2021-03-29 , DOI: 10.1021/jacs.1c01045
Ayesha M Patel ₁ , E Neil G Marsh ₁

Affiliation

Viperin is a broadly conserved radical SAM enzyme that synthesizes the antiviral nucleotide ddhCTP. In higher animals, viperin expression also accelerates the degradation of various cellular and viral proteins necessary for viral replication; however, the details of this process remain largely unknown. Here, we show that viperin activates a component of the protein ubiquitination machinery, which plays an important role in both protein degradation and immune signaling pathways. We demonstrate that viperin binds the E3 ubiquitin ligase, TRAF6, which catalyzes K63-linked ubiquitination associated with immune signaling pathways. Viperin activates ubiquitin transfer by TRAF6–2.5-fold and causes a significant increase in polyubiquitinated forms of TRAF6 that are important for mediating signal transduction. Our observations both imply a role for viperin as an agonist of immune signaling and suggest that viperin may activate other K48-linked E3-ligases involved in targeting proteins for proteasomal degradation.

中文翻译：

抗病毒酶 Viperin 通过 E3 泛素连接酶 TRAF6 激活蛋白质泛素化

Viperin 是一种广泛保守的自由基 SAM 酶，可合成抗病毒核苷酸 ddhCTP。在高等动物中，蛇毒素表达还加速了病毒复制所需的各种细胞和病毒蛋白的降解;然而，这一过程的细节在很大程度上仍然未知。在这里，我们表明蛇毒素激活蛋白质泛素化机制的一个组成部分，该机制在蛋白质降解和免疫信号通路中都起着重要作用。我们证明蝰蛇毒素结合 E3 泛素连接酶 TRAF6，TRAF6 催化与免疫信号通路相关的 K63 连接泛素化。Viperin 以 TRAF6-2.5 倍激活泛素转移，并导致 TRAF6 的多泛素化形式显著增加，这对介导信号转导很重要。我们的观察结果都暗示了蛇穿灵毒素作为免疫信号转导激动剂的作用，并表明蛇穿灵毒素可能会激活其他参与靶向蛋白酶体降解蛋白的 K48 连接的 E3 连接酶。

更新日期：2021-04-08

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