OAS proteins and cGAS: unifying concepts in sensing and responding to cytosolic nucleic acids.
OAS proteins and cGAS: unifying concepts in sensing and responding to cytosolic nucleic acids.
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DOI：
10.1038/nri3719
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发表时间：
2014-08
期刊：
影响因子：
--
通讯作者：
Hopfner KP
中科院分区：
文献类型：
--
作者：
Hornung V;Hartmann R;Ablasser A;Hopfner KP
细胞质中核酸的存在提醒细胞注意病毒感染或自身受损。寡腺苷酸合酶 (OAS) 蛋白和环 GMP-AMP 合酶 (cGAS) 是检测这种危险并促进抗病毒免疫的酶。最近的结构研究表明，这些酶具有共同的作用机制，并且可能具有相同的进化起源。本文的在线版本 (doi:10.1038/nri3719) 包含补充材料，可供授权用户使用。先天免疫领域的最新发现强调了具有相似结构和功能特性的核酸传感蛋白家族的存在。其中包括众所周知的寡腺苷酸合酶 (OAS) 家族蛋白和最近发现的 OAS 同源环 GMP-AMP (cGAMP) 合酶 (cGAS)。 OAS 蛋白和 cGAS 是不依赖于模板的核苷酸转移酶，一旦被胞质中的双链核酸激活，就会产生独特类别的 2'–5' 连接的第二信使分子，这些分子通过不同的机制具有重要的抗病毒功能。 2'–5'-连接的寡腺苷酸通过激活RNase L酶来限制病毒传播，RNase L会降解宿主和病毒RNA，2'-5'-连接的cGAMP激活下游信号通路以诱导从头抗病毒基因表达。在这篇进展文章中，我们描述了 OAS 蛋白和 cGAS 之间惊人的功能和结构相似性，并强调了它们在抗病毒免疫中的作用。本文的在线版本 (doi:10.1038/nri3719) 包含补充材料，可供授权用户使用。
The presence of nucleic acids in the cytosol alerts the cell to viral infection or damaged self. The oligoadenylate synthase (OAS) proteins and cyclic GMP–AMP synthase (cGAS) are enzymes that detect this danger and promote antiviral immunity. Recent structural studies reveal that these enzymes have a common mechanism of action and probably the same evolutionary origin. The online version of this article (doi:10.1038/nri3719) contains supplementary material, which is available to authorized users. Recent discoveries in the field of innate immunity have highlighted the existence of a family of nucleic acid-sensing proteins that have similar structural and functional properties. These include the well-known oligoadenylate synthase (OAS) family proteins and the recently identified OAS homologue cyclic GMP–AMP (cGAMP) synthase (cGAS). The OAS proteins and cGAS are template-independent nucleotidyltransferases that, once activated by double-stranded nucleic acids in the cytosol, produce unique classes of 2′–5′-linked second messenger molecules, which — through distinct mechanisms — have crucial antiviral functions. 2′–5′-linked oligoadenylates limit viral propagation through the activation of the enzyme RNase L, which degrades host and viral RNA, and 2′–5′-linked cGAMP activates downstream signalling pathways to induce de novo antiviral gene expression. In this Progress article, we describe the striking functional and structural similarities between OAS proteins and cGAS, and highlight their roles in antiviral immunity. The online version of this article (doi:10.1038/nri3719) contains supplementary material, which is available to authorized users.
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影响因子：
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