ArticleThe Journal of biological chemistry2013
Identification of binding sites for myeloid differentiation primary response gene 88 (MyD88) and Toll-like receptor 4 in MyD88 adapter-like (Mal).
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 42 citations in OpenAlex.
- Emodin Suppresses NLRP3/GSDMD-induced Inflammation via the TLR4/MyD88/NF-κB Signaling Pathway in Atherosclerosis.Cardiovascular drugs and therapy · 2025Article
- Taohong Siwu decoction ameliorates atherosclerosis in rats possibly through toll-like receptor 4/myeloid differentiation primary response protein 88/nuclear factor-κB signal pathway.Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan · 2024Article
- Cross-Talk between HLA Class I and TLR4 Mediates P-Selectin Surface Expression and Monocyte Capture to Human Endothelial Cells.Journal of immunology (Baltimore, Md. : 1950) · 2022Article
- Article
- Full-Atom Model of the Agonist LPS-Bound Toll-like Receptor 4 Dimer in a Membrane Environment.Chemistry (Weinheim an der Bergstrasse, Germany) · 2021Article
- 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
- Compound LM9, a novel MyD88 inhibitor, efficiently mitigates inflammatory responses and fibrosis in obesity-induced cardiomyopathy.Acta pharmacologica Sinica · 2020Article
- Negative Regulation of TLR Signaling by BCAP Requires Dimerization of Its DBB Domain.Journal of immunology (Baltimore, Md. : 1950) · 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
- Article
- Straightforward Protein-Protein Interaction Interface Mapping via Random Mutagenesis and Mammalian Protein Protein Interaction Trap (MAPPIT).International journal of molecular sciences · 2019Review
- Article
- The Prader-Willi syndrome proteins MAGEL2 and necdin regulate leptin receptor cell surface abundance through ubiquitination pathways.Human molecular genetics · 2017Article
- Structural basis of TIR-domain-assembly formation in MAL- and MyD88-dependent TLR4 signaling.Nature structural & molecular biology · 2017Article
- TIR-only protein RBA1 recognizes a pathogen effector to regulate cell death inProceedings of the National Academy of Sciences of the United States of America · 2017Article
- Conformational dynamics of cancer-associated MyD88-TIR domain mutant L252P (L265P) allosterically tilts the landscape toward homo-dimerization.Protein engineering, design & selection : PEDS · 2016Article
- An extra dimension in protein tagging by quantifying universal proteotypic peptides using targeted proteomics.Scientific reports · 2016Article
- Trapping mammalian protein complexes in viral particles.Nature communications · 2016Article
- Fundamentals of protein interaction network mapping.Molecular systems biology · 2015Review
- A Structural View of Negative Regulation of the Toll-like Receptor-Mediated Inflammatory Pathway.Biophysical journal · 2015Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Upon activation, Toll-like receptor 4 (TLR4) binds adapter proteins, including MyD88 (myeloid differentiation primary response gene 88) and Mal (MyD88 adapter-like) for its signal transduction. TLR4 and the adapter proteins each contain a Toll/Il-1 receptor domain (TIR domain). In this study we used random mutagenesis and the mammalian two-hybrid method MAPPIT (mammalian protein-protein interaction trap) to identify mutations in Mal that disrupt its interaction with TLR4 and/or MyD88. Our study shows that four potential binding sites and the AB-loop in the Mal TIR domain all contribute to formation of the TLR4-Mal-MyD88 complex. Mutations in the symmetrical back-to-back Mal homodimer interface affect Mal homodimerization and interaction with MyD88 and TLR4. Our data suggest that Mal dimerization may lead to formation of potential binding platforms on the top and the side of the Mal dimer that bind MyD88 or TLR4. Mutations that affect the interaction of Mal with MyD88 also affect NF-κB activation induced by Mal overexpression. In MAPPIT, co-expression of the MyD88 TIR domain enhances Mal dimerization and Mal binding to TLR4. Similarly, co-expression of Mal and the MyD88 TIR domain strongly promotes dimerization of the TLR4 intracellular domain in MAPPIT. The different types of TIR-TIR interactions in the TLR4-Mal-MyD88 complex thus show cooperative binding in MAPPIT. We present plausible models for the TIR-TIR interactions in the TLR4-Mal-MyD88 complex.
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