ArticleJournal of immunology (Baltimore, Md. : 1950)2008
Elucidation of the MD-2/TLR4 interface required for signaling by lipid IVa.
Article in Journal of immunology (Baltimore, Md. : 1950), 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 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.
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Who cites it
71 citing papers in PubMed, 119 citations in OpenAlex.
- Cardiolipin inhibits the non-canonical inflammasome by preventing LPS binding to caspase-4/11.The EMBO journal · 2025Article
- Endotoxin-Free Outer Membrane Vesicles for Safe and Modular Anticancer Immunotherapy.ACS synthetic biology · 2025Article
- DAMP-driven trained immunity: metabolic and epigenetic reprogramming in critical illness and chronic inflammation.Frontiers in immunology · 2025Review
- Twelve toll-like receptor (TLR) genes in the family Equidae - comparative genomics, selection and evolution.Veterinary research communications · 2024Article
- Understanding the evolution of immune genes in jawed vertebrates.Journal of evolutionary biology · 2023Review
- TLR4 and MD2 variation among horses with differential TNFα baseline concentrations and response to intravenous lipopolysaccharide infusion.Scientific reports · 2023Article
- Selection Balancing at Innate Immune Genes: Adaptive Polymorphism Maintenance in Toll-Like Receptors.Molecular biology and evolution · 2022Review
- Identification and Characterization of Zebrafish Tlr4 Coreceptor Md-2.Journal of immunology (Baltimore, Md. : 1950) · 2021Article
- Tailored Modulation of Cellular Pro-inflammatory Responses With Disaccharide Lipid A Mimetics.Frontiers in immunology · 2021Article
- Shortening the Lipid A Acyl Chains ofVaccines · 2020Article
- Exploring electrostatic patterns of human, murine, equine and canine TLR4/MD-2 receptors.Innate immunity · 2020Article
- Lipopolysaccharide Recognition in the Crossroads of TLR4 and Caspase-4/11 Mediated Inflammatory Pathways.Frontiers in immunology · 2020Review
- Increasing the Chemical Variety of Small-Molecule-Based TLR4 Modulators: An Overview.Frontiers in immunology · 2020Review
- Saturation of acyl chains converts cardiolipin from an antagonist to an activator of Toll-like receptor-4.Cellular and molecular life sciences : CMLS · 2019Article
- Tracing the evolution of novel features of human Toll-like receptor 4.Protein science : a publication of the Protein Society · 2019Article
- Novel carboxylate-based glycolipids: TLR4 antagonism, MD-2 binding and self-assembly properties.Scientific reports · 2019Article
- Toll-Like Receptor Evolution in Birds: Gene Duplication, Pseudogenization, and Diversifying Selection.Molecular biology and evolution · 2018Article
- Coevolution of the Toll-Like Receptor 4 Complex with Calgranulins and Lipopolysaccharide.Frontiers in immunology · 2018Article
- Toll-like receptor 2 promiscuity is responsible for the immunostimulatory activity of nucleic acid nanocarriers.Journal of controlled release : official journal of the Controlled Release Society · 2017Article
- Computational Approaches to Toll-Like Receptor 4 Modulation.Molecules (Basel, Switzerland) · 2016Review
11 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 2 institutions in 4 countries.
Funding
Abstract
LPS signals through a membrane bound-complex of the lipid binding protein MD-2 and the receptor TLR4. In this study we identify discrete regions in both MD-2 and TLR4 that are required for signaling by lipid IVa, an LPS derivative that is an agonist in horse but an antagonist in humans. We show that changes in the electrostatic surface potential of both MD-2 and TLR4 are required in order that lipid IVa can induce signaling. In MD-2, replacing horse residues 57-66 and 82-89 with the equivalent human residues confers a level of constitutive activity on horse MD-2, suggesting that conformational switching in this protein is likely to be important in ligand-induced activation of MD-2/TLR4. We identify leucine-rich repeat 14 in the C terminus of TLR4 as essential for lipid IVa activation of MD-2/TLR4. Remarkably, we identify a single residue in the glycan-free flank of the horse TLR4 solenoid that confers the ability to signal in response to lipid IVa. These results suggest a mechanism of signaling that involves crosslinking mediated by both MD-2-receptor and receptor-receptor contacts in a model that shows striking similarities to the recently published structure (Cell 130: 1071-1082) of the ligand-bound TLR1/2 ectodomain heterodimer.
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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.