cGAS-STING 通路的 DNA 传感机制。
The cGAS-STING pathway for DNA sensing.
机构信息
Structural Immunobiology Unit, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
出版信息
Mol Cell. 2013 Jul 25;51(2):135-9. doi: 10.1016/j.molcel.2013.07.004.
Abstract
The nucleotidyl transferase cGAS, its second-messenger product cGAMP, and the cGAMP sensor STING form the basic mechanism of DNA sensing in the cytoplasm of mammalian cells. Several new reports now uncover key structural features associated with DNA recognition by cGAS and the catalytic mechanisms of cGAMP generation. Concurrent studies also reveal unique phosphodiester linkages in endogenous cGAMP that distinguish it from microbial cGAMP and other cyclic dinucleotides. Together, these studies provide a new perspective on DNA recognition in the innate immune system.
摘要
核苷酸转移酶 cGAS、其第二信使产物 cGAMP 和 cGAMP 传感器 STING 构成了真核细胞细胞质中 DNA 感应的基本机制。现在有几项新的研究揭示了与 cGAS 的 DNA 识别以及 cGAMP 生成的催化机制相关的关键结构特征。同时进行的研究还揭示了内源性 cGAMP 中的独特磷酸二酯键，使其与微生物 cGAMP 和其他环二核苷酸区分开来。这些研究共同为先天免疫系统中的 DNA 识别提供了新的视角。
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本文引用的文献
1
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Mol Cell. 2013 Jul 25;51(2):226-35. doi: 10.1016/j.molcel.2013.05.022. Epub 2013 Jun 6.
2
Structural mechanism of cytosolic DNA sensing by cGAS.环鸟苷酸合成酶（cGAS）对细胞质 DNA 的感应的结构机制。
Nature. 2013 Jun 20;498(7454):332-7. doi: 10.1038/nature12305. Epub 2013 May 30.
3
cGAS produces a 2'-5'-linked cyclic dinucleotide second messenger that activates STING.cGAS 产生 2'-5'- 连接的环状二核苷酸第二信使，激活 STING。
Nature. 2013 Jun 20;498(7454):380-4. doi: 10.1038/nature12306. Epub 2013 May 30.
4
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5
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6
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8
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9
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