ArticleJournal of immunology (Baltimore, Md. : 1950)2013
An alanine-to-proline mutation in the BB-loop of TLR3 Toll/IL-1R domain switches signalling adaptor specificity from TRIF to MyD88.
Article in Journal of immunology (Baltimore, Md. : 1950), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 38 citations in OpenAlex.
- One adaptor, multiple outcomes: decoding TRIFosome heterogeneity.Biochemical Society transactions · 2026Review
- TLR7 neo-functionalizes to sense dsRNA and trigger antiviral and antibacterial immunity in non-tetrapod vertebrates.iScience · 2023Article
- Re-identification and characterization of grass carpFish and shellfish immunology reports · 2023Article
- Article
- TLR3 forms a highly organized cluster when bound to a poly(I:C) RNA ligand.Nature communications · 2022Article
- A Computational Probe into the Structure and Dynamics of the Full-Length Toll-Like Receptor 3 in a Phospholipid Bilayer.International journal of molecular sciences · 2020Article
- Purifying selection shaping the evolution of the Toll-like receptor 2 TIR domain in brown hares (Lepus europaeus) from Europe and the Middle East.Molecular biology reports · 2020Article
- Subcellular localization of mutated β-catenins with different incidences ofFASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- Thoroughly Remold the Localization and Signaling Pathway of TLR22.Frontiers in immunology · 2019Article
- Toll-like receptor 3 activation impairs excitability and synaptic activity via TRIF signalling in immature rat and human neurons.Neuropharmacology · 2018Article
- Recognition of Double-Stranded RNA and Regulation of Interferon Pathway by Toll-Like Receptor 10.Frontiers in immunology · 2018Article
- Integrative modelling of TIR domain-containing adaptor molecule inducing interferon-β (TRIF) provides insights into its autoinhibited state.Biology direct · 2017Article
- Structure of the Toll/Interleukin-1 Receptor (TIR) Domain of the B-cell Adaptor That Links Phosphoinositide Metabolism with the Negative Regulation of the Toll-like Receptor (TLR) Signalosome.The Journal of biological chemistry · 2017Article
- Simultaneous targeting of MyD88 and Nur77 as an effective approach for the treatment of inflammatory diseases.Drug design, development and therapy · 2016Article
- Interaction between Cannabinoid System and Toll-Like Receptors Controls Inflammation.Mediators of inflammation · 2016Review
- Discovery of small molecule inhibitors of MyD88-dependent signaling pathways using a computational screen.Scientific reports · 2015Article
- Three conserved MyD88-recruiting TLR residues exert different effects on the human TLR4 signaling pathway.Immunologic research · 2015Article
- Innate immune pattern recognition: a cell biological perspective.Annual review of immunology · 2015Review
- Assembly and localization of Toll-like receptor signalling complexes.Nature reviews. Immunology · 2014Review
- Innate immune programing by endotoxin and its pathological consequences.Frontiers in immunology · 2014Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
A functionally important proline residue is highly conserved in the cytosolic Toll/IL-1R signaling domains of human TLRs. The antiviral Toll, TLR3, is unusual because it has alanine instead of proline at this position and is the only human TLR that associates directly with the adaptor molecule TIR domain-containing adaptor inducing IFN-β (TRIF) rather than MyD88. In this article, we report that a mutant TLR3 that substitutes the BB-loop alanine for proline (A795P) enhances NF-κB activation but is incapable of mediating TRIF-dependent IFN response factor 3 responses. Wild-type and A795P TLR3 associate constitutively with both TRIF and MyD88, and activation induces additional binding of TRIF to the wild-type and of MyD88 to the A795P mutant receptors, respectively. In addition, activation of A795P, but not wild-type TLR3, leads to the recruitment of TRAF6, a downstream signal transducer of the MyD88-dependent pathway. These results show that adaptor specificity can be conferred by minimal determinants of the Toll/IL-1R domain.
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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.