ArticleProceedings of the National Academy of Sciences of the United States of America2016
TLR4/MD-2 activation by a synthetic agonist with no similarity to LPS.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 84 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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
84 citing papers in PubMed.
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- AntiPan: a genome-informed in silico pipeline for advancing subunit vaccine discovery against Staphylococcus aureus.Scientific reports · 2026Article
- Probiotic Supplementation Modulates FGFR2 and TLR4 Signaling and Attenuates Chronic Neuroinflammation in an Experimental Stroke Model.Neurochemical research · 2026Article
- Constructing a Pan-Cancer Prognostic Model via Machine Learning Based on Immunogenic Cell Death Genes and Identifying NT5E as a Biomarker in Head and Neck Cancer.Current issues in molecular biology · 2025Article
- Adjuvant activity of a small molecule TLR4 agonist discovered via structure-based virtual screening.Communications biology · 2025Article
- Gut microbiota-derived GlcNAc-MurNAc is a TLR4 agonist that protects the host gut.Nature communications · 2025Article
- FABP7 is increased in progressive multiple sclerosis and induces a pro-inflammatory phenotype in monocytes through a glycolytic switch.Nature communications · 2025Article
- Structural insight into TLR4/MD-2 activation by synthetic LPS mimetics with distinct binding modes.Nature communications · 2025Article
- Antidiabetic and Immunomodulatory Properties of Peptide Fractions from Sacha Inchi Oil Press-Cake.Foods (Basel, Switzerland) · 2025Article
- Structural modifications to pregnane neurosteroids alter inhibition of LPS/Lipid A binding at the MD-2 activation site within the TLR4 signaling complex.Frontiers in immunology · 2025Article
- Novel Inhibitory Actions of Neuroactive Steroid [3α,5α]-3-Hydroxypregnan-20-One on Toll-like Receptor 4-Dependent Neuroimmune Signaling.Biomolecules · 2024Article
- A myeloid differentiation-like protein in partnership with Toll5 from the pest insectProceedings of the National Academy of Sciences of the United States of America · 2024Article
- Unraveling the Protective Role of Oleocanthal and Its Oxidation Product, Oleocanthalic Acid, against Neuroinflammation.Antioxidants (Basel, Switzerland) · 2024Article
- Cyclic-di-GMP induces inflammation and acute lung injury through direct binding to MD2.Clinical and translational medicine · 2024Article
- Salvimulticanol from3 Biotech · 2024Article
- In Vitro Anti-Inflammatory Study of Limonoids Isolated fromCurrent issues in molecular biology · 2024Article
- Immunoinformatic design of a multivalent vaccine againstFrontiers in immunology · 2024Article
- Development of a detection chip for major pathogenic drug-resistant genes and drug targets in bovine respiratory system diseases.Open life sciences · 2024Article
- Small molecule modulators of immune pattern recognition receptors.RSC chemical biology · 2023Review
24 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
- Erratum issued
Authors and funding
16 authors.
Funding
Abstract
Structurally disparate molecules reportedly engage and activate Toll-like receptor (TLR) 4 and other TLRs, yet the interactions that mediate binding and activation by dissimilar ligands remain unknown. We describe Neoseptins, chemically synthesized peptidomimetics that bear no structural similarity to the established TLR4 ligand, lipopolysaccharide (LPS), but productively engage the mouse TLR4 (mTLR4)/myeloid differentiation factor 2 (MD-2) complex. Neoseptin-3 activates mTLR4/MD-2 independently of CD14 and triggers canonical myeloid differentiation primary response gene 88 (MyD88)- and Toll-interleukin 1 receptor (TIR) domain-containing adaptor inducing IFN-beta (TRIF)-dependent signaling. The crystal structure mTLR4/MD-2/Neoseptin-3 at 2.57-Å resolution reveals that Neoseptin-3 binds as an asymmetrical dimer within the hydrophobic pocket of MD-2, inducing an active receptor complex similar to that induced by lipid A. However, Neoseptin-3 and lipid A form dissimilar molecular contacts to achieve receptor activation; hence strong TLR4/MD-2 agonists need not mimic LPS.
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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.