ArticleNucleic acids research2020
Allosteric coupling between Mn2+ and dsDNA controls the catalytic efficiency and fidelity of cGAS.
Article in Nucleic acids research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 96 citations in OpenAlex.
- The cGAS-STING/MITA pathway in innate antiviral immunity and beyond.Cell insight · 2026Review
- Article
- ATP-fueled STING activation of manganese coordinated nanoagonist to boost antitumor immunity.Bioactive materials · 2026Article
- Manganese: biology, physiology and role in disease.Cell discovery · 2026Review
- Protein•DNA mesh assembly drives dsDNA-specific and duplex length-dependent activation of cGAS.bioRxiv : the preprint server for biology · 2026Article
- Mechanisms and Applications of Manganese-Based Materials in Tumor Immunotherapy.Molecules (Basel, Switzerland) · 2026Review
- The Role and Mechanism of the cGAS-STING/NLRP3 Signaling Axis-Regulated p38 MAPK/NF-κB Pathway in Manganese-Induced Tau Aggregation-Mediated Neurotoxicity.Environment & health (Washington, D.C.) · 2026Article
- Biochemical Engineering Perspective on cGAS: From Enzyme Discovery to Potential Industrial Application.Chembiochem : a European journal of chemical biology · 2026Review
- Dimerization-dependent gel-like condensation with dsDNA underpins the activation of human cGAS.Cell reports · 2026Article
- Article
- Tumor-homing cerium nanozyme platform enables coordinated drug release and STING activation for bladder cancer treatment.Journal of nanobiotechnology · 2026Article
- Illumination of Targeting Nanotherapeutics with Precision Eyes: From Optical to Radio-nanotheranostics.Theranostics · 2026Review
- Metal-polyphenol nanomedicines for malignant tumor therapy.Frontiers in chemistry · 2026Review
- cGAS-STING signaling pathway as a therapeutic target in human diseases.Chinese medical journal · 2025Review
- [Research progress on the cGAS-STING signaling pathway in immune-mediated inflammatory diseases in children].Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2025Review
- Unleashing the Potential of Metal Ions in cGAS-STING Activation: Advancing Nanomaterial-Based Tumor Immunotherapy.ACS omega · 2025Review
- Exposure to Manganese Induces Autophagy-Lysosomal Pathway Dysfunction-Mediated Tauopathy by Activating the cGAS-STING Pathway in the Brain.Environment & health (Washington, D.C.) · 2025Article
- Metal Ion Signaling in Biomedicine.Chemical reviews · 2025Review
- Mechanisms and Applications of Manganese-Based Nanomaterials in Tumor Diagnosis and Therapy.Biomaterials research · 2025Review
- Nanomedicines harnessing cGAS-STING pathway: sparking immune revitalization to transform 'cold' tumors into 'hot' tumors.Molecular cancer · 2024Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Cyclic-G/AMP (cGAMP) synthase (cGAS) triggers host innate immune responses against cytosolic double-stranded (ds)DNA arising from genotoxic stress and pathogen invasion. The canonical activation mechanism of cGAS entails dsDNA-binding and dimerization. Here, we report an unexpected activation mechanism of cGAS in which Mn2+ activates monomeric cGAS without dsDNA. Importantly, the Mn2+-mediated activation positively couples with dsDNA-dependent activation in a concerted manner. Moreover, the positive coupling between Mn2+ and dsDNA length-dependent activation requires the cognate ATP/GTP substrate pair, while negative-cooperativity suppresses Mn2+ utilization by either ATP or GTP alone. Additionally, while Mn2+ accelerates the overall catalytic activity, dsDNA length-dependent dimerization specifically accelerates the cyclization of cGAMP. Together, we demonstrate how the intrinsic allostery of cGAS efficiently yet precisely tunes its activity.
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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.