The mechanism of double-stranded DNA sensing through the cGAS-STING pathway. | Academic Article individual record
abstract

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-β 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.

authors
author list (cited authors)
Shu, C., Li, X., & Li, P.
publication date
2014
publisher
Elsevier bv Publisher
published in
keywords
  • Membrane Proteins
  • Cyclic Dinucleotides
  • Type I Interferons
  • Active Transport, Cell Nucleus
  • Signal Transduction
  • Innate Immunity
  • Intracellular Membranes
  • Endoplasmic Reticulum
  • DNA
  • Animals
  • Protein-Serine-Threonine Kinases
  • Transcriptional Activation
  • Pattern Recognition Receptors
  • Phosphorylation
  • Humans
  • Interferon Regulatory Factor-3
  • Nucleotidyltransferases
  • Nucleic Acids
  • Interferon-beta
  • Cell Nucleus
citation count

38