Journal
CYTOKINE & GROWTH FACTOR REVIEWS
Volume 25, Issue 6, Pages 641-648Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.cytogfr.2014.06.006
Keywords
Innate immunity; Pattern recognition receptors; Nucleic acids; Cyclic dinucleotides; Type I interferons
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Funding
- National Institute of Health [AI 087741]
- Welch Foundation [A-1816]
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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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