ArticleBiophysical journal2015
A Structural View of Negative Regulation of the Toll-like Receptor-Mediated Inflammatory Pathway.
Article in Biophysical journal, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
What it found
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Who cites it
42 citing papers in PubMed, 108 citations in OpenAlex.
- Hypothalamic Inflammation as a Critical Link Between Metabolic Dysfunction and Impaired Endometrial Receptivity in Obese Polycystic Ovary Syndrome.Physiological research · 2026Article
- Beyond Negative Regulation: IL-1R8 and IL-1R2 as Novel Immune Checkpoints.European journal of immunology · 2025Review
- Nanocarrier-Based Targeting of Pattern Recognition Receptors as an Innovative Strategy for Enhancing Sepsis Therapy.Advanced healthcare materials · 2025Review
- Pioneer in Molecular Biology: Conformational Ensembles in Molecular Recognition, Allostery, and Cell Function.Journal of molecular biology · 2025Review
- Targeting toll-like receptors: unveiling potential therapeutic strategies for deep vein thrombosis.Frontiers in immunology · 2025Review
- Targeting TLR Signaling Cascades in Systemic Lupus Erythematosus and Rheumatoid Arthritis: An Update.Biomedicines · 2024Article
- Probiotic supplementation for 24 weeks in patients with non-alcoholic steatohepatitis: the PROBILIVER randomized clinical trial.Frontiers in nutrition · 2024Article
- Bilobalide attenuates lipopolysaccharide‑induced HepG2 cell injury by inhibiting TLR4‑NF‑κB signaling via the PI3K/Akt pathway.Experimental and therapeutic medicine · 2024Article
- Structural coverage of the human interactome.Briefings in bioinformatics · 2023Article
- Blockage of CacyBP inhibits macrophage recruitment and improves anti-PD-1 therapy in hepatocellular carcinoma.Journal of experimental & clinical cancer research : CR · 2023Article
- Genomic Structure and Molecular Characterization of Toll-like Receptors in Black Scraper Thamnaconus Modestus and Their Expression Response to Two Types of Pathogens.Marine biotechnology (New York, N.Y.) · 2023Article
- Geniposide protected against cerebral ischemic injury through the anti-inflammatory effect via the NF-κB signaling pathway.Translational neuroscience · 2023Article
- Toll-Like Receptor 4 (TLR4) and AMPK Relevance in Cardiovascular Disease.Advanced pharmaceutical bulletin · 2023Review
- Evaluation of the Effect and Mechanism of Sanhuang Ointment on MRSA Infection in the Skin and Soft Tissue via Network Pharmacology.Infection and drug resistance · 2023Article
- SIGIRR deficiency contributes to CD4 T cell abnormalities by facilitating the IL1/C/EBPβ/TNF-α signaling axis in rheumatoid arthritis.Molecular medicine (Cambridge, Mass.) · 2022Article
- A Splice Switch in SIGIRR Causes a Defect of IL-37-Dependent Anti-Inflammatory Activity in Cystic Fibrosis Airway Epithelial Cells.International journal of molecular sciences · 2022Article
- Pharmacological Effects of Polyphenol Phytochemicals on the Intestinal Inflammation via Targeting TLR4/NF-κB Signaling Pathway.International journal of molecular sciences · 2022Review
- IL-1R8 as Pathoimmunological Marker for Severity of Canine Chronic Enteropathy.Veterinary sciences · 2022Article
- Molecular characterization and functional analysis of DIGIRR from golden pompano (Frontiers in immunology · 2022Article
- Negative Regulation of the IL-1 System by IL-1R2 and IL-1R8: Relevance in Pathophysiology and Disease.Frontiers in immunology · 2022Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 3 countries.
Funding
Abstract
Even though the Toll-like receptor (TLR) pathway is integral to inflammatory defense mechanisms, its excessive signaling may be devastating. Cells have acquired a cascade of strategies to regulate TLR signaling by targeting protein-protein interactions, or ubiquitin chains, but the details of the inhibition mechanisms are still unclear. Here, we provide the structural basis for the regulation of TLR signaling by constructing architectures of protein-protein interactions. Structural data suggest that 1) Toll/IL-1R (TIR) domain-containing regulators (BCAP, SIGIRR, and ST2) interfere with TIR domain signalosome formation; 2) major deubiquitinases such as A20, CYLD, and DUBA prevent association of TRAF6 and TRAF3 with their partners, in addition to removing K63-linked ubiquitin chains that serve as a docking platform for downstream effectors; 3) alternative downstream pathways of TLRs also restrict signaling by competing to bind common partners through shared binding sites. We also performed in silico mutagenesis analysis to characterize the effects of oncogenic mutations on the negative regulators and to observe the cellular outcome (whether there is/is not inflammation). Missense mutations that fall on interfaces and nonsense/frameshift mutations that result in truncated negative regulators disrupt the interactions with the targets, thereby enabling constitutive activation of the nuclear factor-kappa B, and contributing to chronic inflammation, autoimmune diseases, and oncogenesis.
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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.