ArticleProceedings of the National Academy of Sciences of the United States of America2016
Structural basis for concerted recruitment and activation of IRF-3 by innate immune adaptor proteins.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 113 papers.
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Who cites it
113 citing papers in PubMed, 175 citations in OpenAlex.
- Innate immunity: current understandings and future perspectives.Signal transduction and targeted therapy · 2026Review
- The Role of Inflammation and Immunity in Cardiovascular Disease: Molecular Mechanisms and Therapeutic Targets.MedComm · 2026Review
- Molecular basis of SAM-AMP synthesis and degradation in the type III-B CRISPR-Cas system.Nature chemical biology · 2026Article
- Molecular mechanism of 2',3'-cGAMP degradation by monkeypox virus poxin-schlafen protein.The Journal of biological chemistry · 2026Article
- Murine models of pulmonary fibrosis: mechanisms, limitations and translational insights.European respiratory review : an official journal of the European Respiratory Society · 2026Review
- Therapeutic targeting of the cGAS-STING pathway in human disease.The Journal of clinical investigation · 2026Review
- Spotlight on cGAS-STING: role in disease pathogenesis and therapeutic potential.Molecular biomedicine · 2026Review
- Noncanonical IRF3 function mediates STING-dependent pro-inflammatory cytokine production in macrophages.EMBO reports · 2026Article
- A sinomenine derivative protects life-threatening inflammatory injuries via covalently binding to a novel allosteric inhibition site of IRF3.Acta pharmacologica Sinica · 2026Article
- A unique Z-shaped tetramer mediates the autoinhibition of waterfowl STING.PLoS pathogens · 2026Article
- VHL synthetic lethality screens uncover CBF-β as a negative regulator of STING.Nature communications · 2026Article
- Gamma-aminobutyric acid transaminase mediates tumor suppression in renal cell carcinoma through the cGAS-STING-interferon-β axis.Scientific reports · 2026Article
- The cGAS-STING pathway at the crossroads of neuroimmunology: bridging innate immunity to aging and neurodegeneration.Biomarker research · 2026Review
- Molecular Mechanisms of cGAS-STING Axis and Mitochondrial Dysfunction-Related Diseases in Humans: A Comprehensive Review.Current neuropharmacology · 2026Review
- STING signals to NF-κB from late endolysosomal compartments using IRF3 as an adaptor.Nature immunology · 2025Article
- ARIES domains: functional signaling units of type I interferon responses.The FEBS journal · 2025Review
- Cysteine allostery and autoinhibition govern human STING oligomer functionality.Nature chemical biology · 2025Article
- Beyond interferons: Non-canonical roles of MITA/STING.Cell insight · 2025Review
- STING COPII ER Export Trafficking and Signaling Primed by Phosphorylation Switches.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Fish TOLLIP manipulates ATG5 for autophagic degradation of STING to attenuate antiviral interferon responses.PLoS pathogens · 2025Article
53 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
Type I IFNs are key cytokines mediating innate antiviral immunity. cGMP-AMP synthase, ritinoic acid-inducible protein 1 (RIG-I)-like receptors, and Toll-like receptors recognize microbial double-stranded (ds)DNA, dsRNA, and LPS to induce the expression of type I IFNs. These signaling pathways converge at the recruitment and activation of the transcription factor IRF-3 (IFN regulatory factor 3). The adaptor proteins STING (stimulator of IFN genes), MAVS (mitochondrial antiviral signaling), and TRIF (TIR domain-containing adaptor inducing IFN-β) mediate the recruitment of IRF-3 through a conserved pLxIS motif. Here we show that the pLxIS motif of phosphorylated STING, MAVS, and TRIF binds to IRF-3 in a similar manner, whereas residues upstream of the motif confer specificity. The structure of the IRF-3 phosphomimetic mutant S386/396E bound to the cAMP response element binding protein (CREB)-binding protein reveals that the pLxIS motif also mediates IRF-3 dimerization and activation. Moreover, rotavirus NSP1 (nonstructural protein 1) employs a pLxIS motif to target IRF-3 for degradation, but phosphorylation of NSP1 is not required for its activity. These results suggest a concerted mechanism for the recruitment and activation of IRF-3 that can be subverted by viral proteins to evade innate immune responses.
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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.