Crystal structure of ISG54 reveals a novel RNA binding structure and potential functional mechanisms
Crystal structure of ISG54 reveals a novel RNA binding structure and potential functional mechanisms
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ISG54的晶体结构揭示了一种新的RNA结合结构和潜在的功能机制
DOI：
10.1038/cr.2012.111
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发表时间：
2012-09-01
期刊：
影响因子：
44.1
通讯作者：
Liu, Yingfang
中科院分区：
文献类型：
--
作者：
Yang, Zhenlin;Liang, Huanhuan;Liu, Yingfang
干扰素刺激基因56（Interferon-stimulated gene 56，ISG 56）家族成员在阻断病毒复制和调节细胞功能中发挥重要作用，但其分子机制尚不清楚。在这里，我们介绍了ISG 54的晶体结构，ISG 54是一种具有新型RNA结合结构的ISG 56家族蛋白。结构显示ISG 54单体具有9个三肽重复样基序并缔合形成结构域交换的二聚体。C-末端部分折叠成超螺旋结构，并且在其内表面上具有广泛带正电荷的核苷酸结合通道。EMSA结果表明，ISG 54特异性结合一些RNA，如腺苷酸尿苷酸（Au）丰富的RNA，有或没有5′三磷酸化。突变和功能研究表明，这种RNA结合能力对其抗病毒活性很重要。我们的研究结果表明，这种干扰素诱导基因56家族成员的抗病毒活性的新机制。
Interferon-stimulated gene 56 (ISG56) family members play important roles in blocking viral replication and regulating cellular functions, however, their underlying molecular mechanisms are largely unclear. Here, we present the crystal structure of ISG54, an ISG56 family protein with a novel RNA-binding structure. The structure shows that ISG54 monomers have 9 tetratricopeptide repeat-like motifs and associate to form domain-swapped dimers. The C-terminal part folds into a super-helical structure and has an extensively positively-charged nucleotide-binding channel on its inner surface. EMSA results show that ISG54 binds specifically to some RNAs, such as adenylate uridylate (AU)-rich RNAs, with or without 5′ triphosphorylation. Mutagenesis and functional studies show that this RNA-binding ability is important to its antiviral activity. Our results suggest a new mechanism underlying the antiviral activity of this interferon-inducible gene 56 family member.