ArticleThe Journal of biological chemistry2012
Identification of interaction sites for dimerization and adapter recruitment in Toll/interleukin-1 receptor (TIR) domain of Toll-like receptor 4.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 68 citations in OpenAlex.
- Emerging host-directed strategies for overcoming drug resistance and immune evasion in Staphylococcus aureus infections.Journal of advanced research · 2026Review
- TLR2 and TLR4 bridge physiological and pathological inflammation in the reproductive system.Communications biology · 2025Review
- Identification of novel amino acid variants in the Han Chinese population that impair toll-like receptor 4 signaling and confer hyporesponsiveness to lipopolysaccharide.Frontiers in immunology · 2025Article
- Acetylation of TIR domains in the TLR4-Mal-MyD88 complex regulates immune responses in sepsis.The EMBO journal · 2024Article
- A novel missense compound heterozygous variant in TLR1 gene is associated with susceptibility to rheumatoid arthritis - structural perspective and functional annotations.Clinical rheumatology · 2023Article
- TLR4 phosphorylation at tyrosine 672 activates the ERK/c-FOS signaling module for LPS-induced cytokine responses in macrophages.European journal of immunology · 2023Article
- Modeling of Transmembrane Domain and Full-Length TLRs in Membrane Models.Methods in molecular biology (Clifton, N.J.) · 2023Article
- TRPC channels blockade abolishes endotoxemic cardiac dysfunction by hampering intracellular inflammation and CaNature communications · 2022Article
- Article
- Full-Atom Model of the Agonist LPS-Bound Toll-like Receptor 4 Dimer in a Membrane Environment.Chemistry (Weinheim an der Bergstrasse, Germany) · 2021Article
- TLR4 signaling and macrophage inflammatory responses are dampened by GIV/Girdin.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- TLR4-Targeting Therapeutics: Structural Basis and Computer-Aided Drug Discovery Approaches.Molecules (Basel, Switzerland) · 2020Review
- Enzymatic Functions for Toll/Interleukin-1 Receptor Domain Proteins in the Plant Immune System.Frontiers in genetics · 2020Review
- A cell-penetrating peptide blocks Toll-like receptor-mediated downstream signaling and ameliorates autoimmune and inflammatory diseases in mice.Experimental & molecular medicine · 2019Article
- Elevated pre-activation basal level of nuclear NF-κB in native macrophages accelerates LPS-induced translocation of cytosolic NF-κB into the cell nucleus.Scientific reports · 2019Article
- Insight into Phosphatidylinositol-Dependent Membrane Localization of the Innate Immune Adaptor Protein Toll/Interleukin 1 Receptor Domain-Containing Adaptor Protein.Frontiers in immunology · 2018Article
- Computational Insight Into the Structural Organization of Full-Length Toll-Like Receptor 4 Dimer in a Model Phospholipid Bilayer.Frontiers in immunology · 2018Article
- Host species adaptation of TLR5 signalling and flagellin recognition.Scientific reports · 2017Article
- Structural basis of TIR-domain-assembly formation in MAL- and MyD88-dependent TLR4 signaling.Nature structural & molecular biology · 2017Article
- SARM1-specific motifs in the TIR domain enable NAD+ loss and regulate injury-induced SARM1 activation.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Toll-like receptor signaling requires interactions of the Toll/IL-1 receptor (TIR) domains of the receptor and adapter proteins. Using the mammalian protein-protein interaction trap strategy, homology modeling, and site-directed mutagenesis, we identify the interaction surfaces in the TLR4 TIR domain for the TLR4-TLR4, TLR4-MyD88 adapter-like (MAL), and TLR4-TRIF-related adapter molecule (TRAM) interaction. Two binding sites are equally important for TLR4 dimerization and adapter recruitment. In a model based on the crystal structure of the dimeric TLR10 TIR domain, the first binding site mediates TLR4-TLR4 TIR-TIR interaction. Upon dimerization, two identical second binding sites of the TLR4 TIR domain are juxtaposed and form an extended binding platform for both MAL and TRAM. In our mammalian protein-protein interaction trap assay, MAL and TRAM compete for binding to this platform. Our data suggest that adapter binding can stabilize the TLR4 TIR dimerization.
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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.