The mechanism of double-stranded DNA sensing through the cGAS-STING pathway.
Cytokine Growth Factor Rev
; 25(6): 641-8, 2014 Dec.
Article
em En
| MEDLINE
| ID: mdl-25007740
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-ß 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.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
DNA
/
Transdução de Sinais
/
Proteínas de Membrana
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Nucleotidiltransferases
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Cytokine Growth Factor Rev
Assunto da revista:
ALERGIA E IMUNOLOGIA
/
BIOQUIMICA
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
Estados Unidos
País de publicação:
Reino Unido