ArticleJournal of immunology (Baltimore, Md. : 1950)2011
Targeting TLR4 signaling by TLR4 Toll/IL-1 receptor domain-derived decoy peptides: identification of the TLR4 Toll/IL-1 receptor domain dimerization interface.
Article in Journal of immunology (Baltimore, Md. : 1950), 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 1 of them a synthesis that pooled it.
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Who cites it
47 citing papers in PubMed, 1 synthesis or guideline pooled it, 77 citations in OpenAlex.
- TIR domain proteins: regulatory mechanisms in the tumor immune microenvironment, clinical translation strategies, and prospects for precision therapy applications.Frontiers in immunology · 2025Pooled it
- Immunoinformatic-driven design and evaluation of multi-epitope mRNA vaccine targeting HIV-1 gp120.Frontiers in immunology · 2025Article
- Massively Parallel Screening of Toll/Interleukin-1 Receptor (TIR)-Derived Peptides Reveals Multiple Toll-Like Receptors (TLRs)-Targeting Immunomodulatory Peptides.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Real-time monitoring with iTLR4 assay identifies ligand-dependent TLR4-TLR4 conformational dynamics.Frontiers in immunology · 2025Article
- TLR5-Derived, TIR-Interacting Decoy Peptides to Inhibit TLR Signaling.Journal of immunology (Baltimore, Md. : 1950) · 2023Article
- Dimerization of Transmembrane Proteins in Cancer Immunotherapy.Membranes · 2023Review
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- Full-Atom Model of the Agonist LPS-Bound Toll-like Receptor 4 Dimer in a Membrane Environment.Chemistry (Weinheim an der Bergstrasse, Germany) · 2021Article
- Light-Inducible Spatio-Temporal Control of TLR4 and NF-κB-Gluc Reporter in Human Pancreatic Cell Line.International journal of molecular sciences · 2021Article
- A mouse model of human TLR4 D299G/T399I SNPs reveals mechanisms of altered LPS and pathogen responses.The Journal of experimental medicine · 2021Article
- Toll-Like Receptors: General Molecular and Structural Biology.Journal of immunology research · 2021Review
- Frontline Science: Targeting the TLR7 signalosome assembly.Journal of leukocyte biology · 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
- Targeting the TLR signalosome with TIR domain-derived cell-permeable decoy peptides: the current state and perspectives.Innate immunity · 2020Review
- Recent clinical trends in Toll-like receptor targeting therapeutics.Medicinal research reviews · 2019Review
- A cell-penetrating peptide blocks Toll-like receptor-mediated downstream signaling and ameliorates autoimmune and inflammatory diseases in mice.Experimental & molecular medicine · 2019Article
- Bacterial TIR domain-derived peptides inhibit innate immune signaling and catabolic responses in chondrocyte.Molecular biology reports · 2019Article
- INH14, a Small-Molecule Urea Derivative, Inhibits the IKKα/β-Dependent TLR Inflammatory Response.Chembiochem : a European journal of chemical biology · 2019Article
- TRAF3-interacting JNK-activating modulator promotes inflammation by stimulating translocation of Toll-like receptor 4 to lipid rafts.The Journal of biological chemistry · 2019Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Agonist-induced dimerization of TLR4 Toll/IL-1R (TIR) domains initiates intracellular signaling. Therefore, identification of the TLR4-TIR dimerization interface is one key to the rational design of therapeutics that block TLR4 signaling. A library of cell-permeating decoy peptides, each of which represents a nonfragmented patch of the TLR4 TIR surface, was designed such that the peptides entirely encompass the TLR4 TIR surface. Each peptide was synthesized in tandem with a cell-permeating Antennapedia homeodomain sequence and tested for the ability to inhibit early cytokine mRNA expression and MAPK activation in LPS-stimulated primary murine macrophages. Five peptides--4R1, 4R3, 4BB, 4R9, and 4αE--potently inhibited all manifestations of TLR4, but not TLR2 signaling. When tested for their ability to bind directly to TLR4 TIR by Förster resonance energy transfer using time-resolved fluorescence spectroscopy, Bodipy-TMR-X-labeled 4R1, 4BB, and 4αE quenched fluorescence of TLR4-Cerulean expressed in HeLa or HEK293T cells, whereas 4R3 was partially active, and 4R9 was least active. These findings suggest that the area between the BB loop of TLR4 and its fifth helical region mediates TLR4 TIR dimerization. Moreover, our data provide direct evidence for the utility of the decoy peptide approach, in which peptides representing various surface-exposed segments of a protein are initially probed for the ability to inhibit protein function, and then their specific targets are identified by Förster resonance energy transfer to define recognition sites in signaling proteins that may be targeted therapeutically to disrupt functional transient protein interactions.
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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.