ArticlePloS one2011
In silico approach to inhibition of signaling pathways of Toll-like receptors 2 and 4 by ST2L.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 56 citations in OpenAlex.
- Trial
- Toll-like receptors in innate immunity and inflammation: from fundamental biology to clinic insights.Immunity & inflammation · 2026Review
- Role of toll-like receptor in the pathogenesis of oral cancer.Cell biochemistry and biophysics · 2024Review
- Comparative analyses of bat genomes identify distinct evolution of immunity in Old World fruit bats.Science advances · 2023Article
- Sperm activate TLR2/TLR1 heterodimerization to induce a weak proinflammatory response in the bovine uterus.Frontiers in immunology · 2023Article
- Toll-Like Receptors in Acute Kidney Injury.International journal of molecular sciences · 2021Review
- Toll-like receptors in sepsis-associated cytokine storm and their endogenous negative regulators as future immunomodulatory targets.International immunopharmacology · 2020Review
- TLR4 signaling and macrophage inflammatory responses are dampened by GIV/Girdin.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Interaction between MyD88, TIRAP and IL1RL1 against Helicobacter pylori infection.Scientific reports · 2020Article
- Evolution of In Silico Strategies for Protein-Protein Interaction Drug Discovery.Molecules (Basel, Switzerland) · 2018Review
- IL-33/ST2 signalling and crosstalk with FcεRI and TLR4 is targeted by the parasitic worm product, ES-62.Scientific reports · 2018Article
- DHSpred: support-vector-machine-based human DNase I hypersensitive sites prediction using the optimal features selected by random forest.Oncotarget · 2018Article
- PIP-EL: A New Ensemble Learning Method for Improved Proinflammatory Peptide Predictions.Frontiers in immunology · 2018Article
- iBCE-EL: A New Ensemble Learning Framework for Improved Linear B-Cell Epitope Prediction.Frontiers in immunology · 2018Article
- iGHBP: Computational identification of growth hormone binding proteins from sequences using extremely randomised tree.Computational and structural biotechnology journal · 2018Article
- AIPpred: Sequence-Based Prediction of Anti-inflammatory Peptides Using Random Forest.Frontiers in pharmacology · 2018Article
- PVP-SVM: Sequence-Based Prediction of Phage Virion Proteins Using a Support Vector Machine.Frontiers in microbiology · 2018Article
- MLACP: machine-learning-based prediction of anticancer peptides.Oncotarget · 2017Article
- Structure-Activity Relationship in TLR4 Mutations: Atomistic Molecular Dynamics Simulations and Residue Interaction Network Analysis.Scientific reports · 2017Article
- Macrophages and the Recovery from Acute and Chronic Inflammation.Annual review of physiology · 2017Review
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
Toll-like receptors (TLRs) activate a potent immunostimulatory response. There is clear evidence that overactivation of TLRs leads to infectious and inflammatory diseases. Recent biochemical studies have shown that the membrane-bound form of ST2 (ST2L), a member of the Toll-like/IL-1 receptor superfamily, negatively regulates MyD88-dependent TLR signaling pathways by sequestrating the adapters MyD88 and Mal (TIRAP). Specifically, ST2L attenuates the recruitment of Mal and MyD88 adapters to their receptors through its intracellular TIR domain. Thus, ST2L is a potent molecule that acts as a key regulator of endotoxin tolerance and modulates innate immunity. So far, the inhibitory mechanism of ST2L at the molecular level remains elusive. To develop a working hypothesis for the interactions between ST2L, TLRs (TLR1, 2, 4, and 6), and adapter molecules (MyD88 and Mal), we constructed three-dimensional models of the TIR domains of TLR4, 6, Mal, and ST2L based on homology modeling. Since the crystal structures of the TIR domains of TLR1, 2 as well as the NMR solution structure of MyD88 are known, we utilized these structures in our analysis. The TIR domains of TLR1, 2, 4, 6, MyD88, Mal and ST2L were subjected to molecular dynamics (MD) simulations in an explicit solvent environment. The refined structures obtained from the MD simulations were subsequently used in molecular docking studies to probe for potential sites of interactions. Through protein-protein docking analysis, models of the essential complexes involved in TLR2 and 4 signaling and ST2L inhibiting processes were developed. Our results suggest that ST2L may exert its inhibitory effect by blocking the molecular interface of Mal and MyD88 adapters mainly through its BB-loop region. Our predicted oligomeric signaling models may provide a basis for the understanding of the assembly process of TIR domain interactions, which has thus far proven to be difficult via in vivo studies.
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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.