ArticleScientific reports2017
Membrane targeting of TIRAP is negatively regulated by phosphorylation in its phosphoinositide-binding motif.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 17 citations in OpenAlex.
- Quantitative Modeling of TLR Signaling Reveals Missing Negative Feedback Guiding Identification of TANK-IKKε Checkpoint.bioRxiv : the preprint server for biology · 2026Article
- Review
- Negative regulators antagonizing antitumor innate immune pathways in lung cancer immune evasion.Frontiers in immunology · 2026Review
- Novel Inhibitory Actions of Neuroactive Steroid [3α,5α]-3-Hydroxypregnan-20-One on Toll-like Receptor 4-Dependent Neuroimmune Signaling.Biomolecules · 2024Article
- A detailed molecular network map and model of the NLRP3 inflammasome.Frontiers in immunology · 2023Review
- NLRP3 Inflammasome Priming and Activation Are Regulated by a Phosphatidylinositol-Dependent Mechanism.ImmunoHorizons · 2022Article
- Knockdown of Transmembrane Protein 150A (Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research · 2022Article
- Phosphatases in toll-like receptors signaling: the unfairly-forgotten.Cell communication and signaling : CCS · 2021Review
- TIRAP in the Mechanism of Inflammation.Frontiers in immunology · 2021Review
- A peptide derived from the core β-sheet region of TIRAP decoys TLR4 and reduces inflammatory and autoimmune symptoms in murine models.EBioMedicine · 2020Article
- Paradoxical Roles of the MAL/Tirap Adaptor in Pathologies.Frontiers in immunology · 2020Review
- Preferential phosphatidylinositol 5-phosphate binding contributes to a destabilization of the VHS domain structure of Tom1.Scientific reports · 2019Article
- Insight into Phosphatidylinositol-Dependent Membrane Localization of the Innate Immune Adaptor Protein Toll/Interleukin 1 Receptor Domain-Containing Adaptor Protein.Frontiers in immunology · 2018Article
- Solution structure of the TLR adaptor MAL/TIRAP reveals an intact BB loop and supports MAL Cys91 glutathionylation for signaling.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 3 countries.
Funding
Abstract
Pathogen-activated Toll-like receptors (TLRs), such as TLR2 and TLR4, dimerize and move laterally across the plasma membrane to phosphatidylinositol (4,5)-bisphosphate-enriched domains. At these sites, TLRs interact with the TIR domain-containing adaptor protein (TIRAP), triggering a signaling cascade that leads to innate immune responses. Membrane recruitment of TIRAP is mediated by its phosphoinositide (PI)-binding motif (PBM). We show that TIRAP PBM transitions from a disordered to a helical conformation in the presence of either zwitterionic micelles or monodispersed PIs. TIRAP PBM bound PIs through basic and nonpolar residues with high affinity, favoring a more ordered structure. TIRAP is phosphorylated at Thr28 within its PBM, which leads to its ubiquitination and degradation. We demonstrate that phosphorylation distorts the helical structure of TIRAP PBM, reducing PI interactions and cell membrane targeting. Our study provides the basis for TIRAP membrane insertion and the mechanism by which it is removed from membranes to avoid sustained innate immune responses.
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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.