ArticleCell reports2014
The cytosolic DNA sensor cGAS forms an oligomeric complex with DNA and undergoes switch-like conformational changes in the activation loop.
Article in Cell reports, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 308 papers, 1 of them a synthesis that pooled it.
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Who cites it
308 citing papers in PubMed, 1 synthesis or guideline pooled it, 484 citations in OpenAlex.
- cGAS in nucleus: The link between immune response and DNA damage repair.Frontiers in immunology · 2022Pooled it
- Nanoadjuvant-based membrane poration boosts antitumor immunity via modulating mitochondrial metabolism to downregulate PD-L1 and upregulate STING.Bioactive materials · 2027Article
- The cGAS-STING pathway in inflammaging and neuroinflammation.Science China. Life sciences · 2026Review
- Low-dose radiotherapy as an immunomodulator in cancer: dose-specific mechanisms and hybrid high-dose/low-dose strategies.Biomarker research · 2026Review
- cGAS-STING signaling in the anterior cingulate cortex modulates electroacupuncture analgesia in a rat neuropathic pain model.The Korean journal of pain · 2026Article
- The NLRP3 inflammasome at the crossroads of innate immune signaling and cell death.Cellular & molecular immunology · 2026Review
- Dynamic phosphorylation of cGAS by DNA-PKcs and PPP1CC balances DNA repair and innate immunity.Medical oncology (Northwood, London, England) · 2026Article
- Inhibition by ATP regulates the activity of a CBASS anti-phage nucleotide cyclase.The Biochemical journal · 2026Article
- Geometry-Programmable Living Immunomaterials for Spatial Control of Innate Immune Signaling.Advanced materials (Deerfield Beach, Fla.) · 2026Article
- DNA Sensing and Neuroinflammation: Mechanistic Insights into cGAS-STING Biology and Therapeutic Translation in Age-Related Neurodegenerative Diseases.Molecular neurobiology · 2026Review
- Emerging roles of the cGAS/STING pathway in cardiovascular diseases.The Journal of clinical investigation · 2026Review
- Protein•DNA mesh assembly drives dsDNA-specific and duplex length-dependent activation of cGAS.bioRxiv : the preprint server for biology · 2026Article
- Extracellular cGAMP in health and disease.Molecular biomedicine · 2026Review
- Enterovirus A71 3AB protein facilitates immune evasion by blocking cGAS recognition of mtDNA.EMBO reports · 2026Article
- Inhibition of the Microglial cGAS-STING Pathway Improves Neurological Deficits and Long-Term Hydrocephalus Symptoms in Mice with Intraventricular Hemorrhage.Molecular neurobiology · 2026Article
- Immune signaling and function in neurodegeneration.The Journal of clinical investigation · 2026Review
- Machine Learning-Guided Engineering of Protein Phase Separation Properties in Immune Regulation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- STING Mediates Microglial Polarization to Promote Neuroinflammation in Epilepsy-Related Cognitive Dysfunction.Neurochemical research · 2026Article
- Biochemical Engineering Perspective on cGAS: From Enzyme Discovery to Potential Industrial Application.Chembiochem : a European journal of chemical biology · 2026Review
- Advances in Elucidating the Mitochondrial DNA Mechanisms Underlying Ozone-Induced Inflammation.Toxics · 2026Review
248 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
The presence of DNA in the cytoplasm is a danger signal that triggers immune and inflammatory responses. Cytosolic DNA binds to and activates cyclic GMP-AMP (cGAMP) synthase (cGAS), which produces the second messenger cGAMP. cGAMP binds to the adaptor protein STING and activates a signaling cascade that leads to the production of type I interferons and other cytokines. Here, we report the crystal structures of human cGAS in its apo form, representing its autoinhibited conformation as well as in its cGAMP- and sulfate-bound forms. These structures reveal switch-like conformational changes of an activation loop that result in the rearrangement of the catalytic site. The structure of DNA-bound cGAS reveals a complex composed of dimeric cGAS bound to two molecules of DNA. Functional analyses of cGAS mutants demonstrate that both the protein-protein interface and the two DNA binding surfaces are critical for cGAS activation. These results provide insights into the mechanism of DNA sensing by cGAS.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.