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Related Experiment Video

Updated: May 9, 2026

Stimulation of Cytoplasmic DNA Sensing Pathways In Vitro and In Vivo

Stimulation of Cytoplasmic DNA Sensing Pathways In Vitro and In Vivo

Published on: September 18, 2014

The cGAS-STING pathway for DNA sensing.

T Sam Xiao¹, Katherine A Fitzgerald

¹Structural Immunobiology Unit, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.

|July 23, 2013

Summary

The cyclic GMP-AMP synthase (cGAS) enzyme and its sensor STING are key to cellular DNA detection. New research reveals cGAS structural details for DNA binding and cGAMP synthesis, enhancing innate immunity understanding.

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Area of Science:

Immunology
Molecular Biology
Biochemistry

Background:

The cyclic GMP-AMP synthase (cGAS), its product cyclic GMP-AMP (cGAMP), and the cGAMP sensor STING mediate cytoplasmic DNA sensing in mammals.
This pathway is crucial for initiating innate immune responses against foreign or self-DNA.

Purpose of the Study:

To elucidate the structural basis of DNA recognition by cGAS.
To investigate the catalytic mechanisms underlying cGAMP synthesis by cGAS.
To characterize the unique structural features of endogenous cGAMP.

Main Methods:

X-ray crystallography and cryo-electron microscopy to determine cGAS-DNA complex structures.
Biochemical assays to study cGAS enzymatic activity and cGAMP formation.
Mass spectrometry to analyze the phosphodiester linkages in cGAMP.

Main Results:

Detailed structural insights into how cGAS binds to DNA.
Characterization of the catalytic steps involved in cGAMP production.
Identification of distinct phosphodiester linkages in endogenous cGAMP compared to microbial analogs.

Conclusions:

These findings provide a deeper understanding of the cGAS-STING pathway's molecular mechanisms.
The structural and biochemical data offer new perspectives on innate immune sensing of DNA.
Understanding these details may inform therapeutic strategies targeting DNA-mediated inflammatory diseases.