ArticlePloS one2012
Structural insights into TIR domain specificity of the bridging adaptor Mal in TLR4 signaling.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 78 citations in OpenAlex.
- Roles of TIR domain-containing adaptor protein in tumor: Inflammation and immune regulation via toll-like receptor signaling.The Journal of international medical research · 2026Review
- Structural Mechanism of Receptor-Triggered MyD88 Oligomeric Assembly in Innate Immune Signaling.Nature communications · 2026Article
- Oridonin attenuates TLR4-driven inflammation and autophagy in LPS-stimulated enteric glial cells: anFrontiers in cellular neuroscience · 2026Article
- o-Vanillin binds covalently to MAL/TIRAP Lys-210 but independently inhibits TLR2.Journal of enzyme inhibition and medicinal chemistry · 2024Article
- MyD88 protein destabilization mitigates NF-κB-dependent protection against macrophage apoptosis.Cell communication and signaling : CCS · 2024Article
- Review
- 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
- Ammonia transporter RhBG initiates downstream signaling and functional responses by activating NFκB.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Article
- Article
- Human and Bacterial Toll-Interleukin Receptor Domains Exhibit Distinct Dynamic Features and Functions.Molecules (Basel, Switzerland) · 2022Article
- TIRAP-mediated activation of p38 MAPK in inflammatory signaling.Scientific reports · 2022Article
- Lys694Arg polymorphism leads to blunted responses to LPS by interfering TLR4 with recruitment of MyD88.Innate immunity · 2021Article
- TIRAP in the Mechanism of Inflammation.Frontiers in immunology · 2021Review
- Negative Regulation of TLR Signaling by BCAP Requires Dimerization of Its DBB Domain.Journal of immunology (Baltimore, Md. : 1950) · 2020Article
- A survey of TIR domain sequence and structure divergence.Immunogenetics · 2020Article
- A peptide derived from the core β-sheet region of TIRAP decoys TLR4 and reduces inflammatory and autoimmune symptoms in murine models.EBioMedicine · 2020Article
- TIRAP p.R81C is a novel lymphoma risk variant which enhances cell proliferationHaematologica · 2019Article
- Structure of a prokaryotic SEFIR domain reveals two novel SEFIR-SEFIR interaction modes.Journal of structural biology · 2018Article
- Development of a Novel Backbone Cyclic Peptide Inhibitor of the Innate Immune TLR/IL1R Signaling Protein MyD88.Scientific reports · 2018Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
MyD88 adaptor-like protein (Mal) is a crucial adaptor that acts as a bridge to recruit the MyD88 molecule to activated TLR4 receptors in response to invading pathogens. The specific assembly of the Toll/interleukin-1 receptor (TIR) domains of TLR4, Mal and MyD88 is responsible for proper signal transduction in the TLR4 signaling pathway. However, the molecular mechanism for the specificity of these TIR domains remains unclear. Here, we present the crystal structure of the TIR domain of the human Mal molecule (Mal-TIR) at a resolution of 2.4 Å. Unexpectedly, Mal-TIR exhibits an extraordinarily long AB loop, but no αB helix or BB loop, distinguishing it from other TIR domains. More importantly, the Mal-TIR AB loop is capable of mediating direct binding to the TIR domains of TLR4 and MyD88 simultaneously. We also found that Mal-TIR can form a back-to-back dimer that may resemble the dimeric assembly of the entire Mal molecule. Our data demonstrate the bridge role of the Mal-TIR domain and provide important information about TIR domain specificity.
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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.