The mechanism of double-stranded DNA sensing through the cGAS-STING pathway

被引：78
作者：
Shu, Chang [1 ]
Li, Xin [1 ]
Li, Pingwei [1 ]
机构：
[1] Texas A&M Univ, Dept Biochem & Biophys, College Stn, TX 77843 USA
来源：
CYTOKINE & GROWTH FACTOR REVIEWS | 2014年 / 25卷 / 06期
关键词：
Innate immunity; Pattern recognition receptors; Nucleic acids; Cyclic dinucleotides; Type I interferons; CYCLIC GMP-AMP; INNATE IMMUNE SENSOR; DI-GMP; ANTIVIRAL RESPONSE; STRUCTURAL BASIS; RECOGNITION; SYNTHASE; FAMILY; PHOSPHORYLATION; 2ND-MESSENGER;
D O I：
10.1016/j.cytogfr.2014.06.006
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
Microbial nucleic acids induce potent innate immune responses by stimulating the expression of type I interferons. Cyclic GMP-AMP synthase (cGAS) is a cytosolic dsDNA sensor mediating the innate immunity to microbial DNA. cGAS is activated by dsDNA and catalyze the synthesis of a cyclic dinucleotide cGAMP with 2',5' and 3',5'phosphodiester linkages. cGAMP binds to the adaptor STING located on the endoplasmic reticulum membrane and mediates the recruitment and activation of the protein kinase TBK1 and transcription factor IRF3. Phosphorylated IRF3 translocates to the nucleus and initiates the transcription of the IFN-beta gene. The crystal structures of cGAS and its complex with dsDNA, STING and its complex with various cyclic dinucleotides have been determined recently. Here we summarize the results from these structural studies and provide an overview about the mechanism of cGAS activation by dsDNA, the catalytic mechanism of cGAS, and the structural basis of STING activation by cGAMP. Published by Elsevier Ltd.
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页码：641 / 648
页数：8
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