ArticleScientific reports2015
The Architecture of the TIR Domain Signalosome in the Toll-like Receptor-4 Signaling Pathway.
Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
73 citing papers in PubMed, 113 citations in OpenAlex.
- Review
- TLR ligands as immunomodulators: mechanistic insights and therapeutic potential in infectious and inflammatory diseases.Molecular biology reports · 2026Review
- Lumican-TLR4 interaction accelerates hepatic fibrosis by activating hepatic stellate cells.Hepatology communications · 2026Article
- Protective effect of hesperetin against myelosuppression and splenic inflammation via modulating TLR4/MYD88/NF-κB signaling: molecular docking and experimental validation.Frontiers in pharmacology · 2026Article
- MyD88 Contributes to TLR3-Mediated NF-κB Activation and Cytokine Production in Macrophages.Cells · 2025Article
- Pioneer in Molecular Biology: Conformational Ensembles in Molecular Recognition, Allostery, and Cell Function.Journal of molecular biology · 2025Review
- Role of TLRs as signaling cascades to combat infectious diseases: a review.Cellular and molecular life sciences : CMLS · 2025Review
- Novel Inhibitory Actions of Neuroactive Steroid [3α,5α]-3-Hydroxypregnan-20-One on Toll-like Receptor 4-Dependent Neuroimmune Signaling.Biomolecules · 2024Article
- Interactions Between Bovine Respiratory Syncytial Virus and Cattle: Aspects of Pathogenesis and Immunity.Viruses · 2024Review
- Acetylation of TIR domains in the TLR4-Mal-MyD88 complex regulates immune responses in sepsis.The EMBO journal · 2024Article
- Uncovering the impact of alcohol on internal organs and reproductive health: Exploring TLR4/NF-kB and CYP2E1/ROS/Nrf2 pathways.Animal models and experimental medicine · 2024Review
- Vaccine adjuvants for infectious disease in the clinic.Bioengineering & translational medicine · 2024Review
- 2,4'-Dihydroxybenzophenone: A Promising Anti-Inflammatory Agent Targeting Toll-like Receptor 4/Myeloid Differentiation Factor 2-Mediated Mitochondrial Reactive Oxygen Species Production during Lipopolysaccharide-Induced Systemic Inflammation.ACS pharmacology & translational science · 2024Article
- Article
- TIR domains of TLR family-from the cell culture to the protein sample for structural studies.PloS one · 2024Article
- Recent advances in different interactions between toll-like receptors and hepatitis B infection: a review.Frontiers in immunology · 2024Review
- IRF3 function and immunological gaps in sepsis.Frontiers in immunology · 2024Review
- Toll-like receptor 4 pathway evolutionary trajectory and functional emergence.Frontiers in immunology · 2024Article
- Novel Time-dependent Multi-omics Integration in Sepsis-associated Liver Dysfunction.Genomics, proteomics & bioinformatics · 2023Article
- Toll-like receptor 4 (TLR4): new insight immune and aging.Immunity & ageing : I & A · 2023Review
13 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 4 institutions in 3 countries.
Funding
Abstract
Activated Toll-like receptors (TLRs) cluster in lipid rafts and induce pro- and anti-tumor responses. The organization of the assembly is critical to the understanding of how these key receptors control major signaling pathways in the cell. Although several models for individual interactions were proposed, the entire TIR-domain signalosome architecture has not been worked out, possibly due to its complexity. We employ a powerful algorithm, crystal structures and experimental data to model the TLR4 and its cluster. The architecture that we obtain with 8 MyD88 molecules provides the structural basis for the MyD88-templated myddosome helical assembly and receptor clustering; it also provides clues to pro- and anti-inflammatory signaling pathways branching at the signalosome level to Mal/MyD88 and TRAM/TRIF pro- and anti-inflammatory pathways. The assembly of MyD88 death domain (DD) with TRAF3 (anti-viral/anti-inflammatory) and TRAF6 (pro-inflammatory) suggest that TRAF3/TRAF6 binding sites on MyD88 DD partially overlap, as do IRAK4 and FADD. Significantly, the organization illuminates mechanisms of oncogenic mutations, demonstrates that almost all TLR4 parallel pathways are competitive and clarifies decisions at pathway branching points. The architectures are compatible with the currently-available experimental data and provide compelling insights into signaling in cancer and inflammation pathways.
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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.