ArticlePLoS pathogens2017
The role of the C-terminal D0 domain of flagellin in activation of Toll like receptor 5.
Article in PLoS pathogens, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 1 of them a synthesis that pooled it.
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Who cites it
35 citing papers in PubMed, 1 synthesis or guideline pooled it, 68 citations in OpenAlex.
- Short Chain Fatty Acids and Fecal Microbiota Abundance in Humans with Obesity: A Systematic Review and Meta-Analysis.Nutrients · 2019Pooled it
- Toll-like receptors in fish: evolution, structure, immune signaling, and translational prospects for adjuvant-based vaccine design in aquaculture.Frontiers in immunology · 2026Review
- Divergent immune responses to commensal bacteria bearing distinct motility signatures.Science immunology · 2025Article
- Development of a vaccine construct againstNAR genomics and bioinformatics · 2025Article
- Immunoinformatics-driven design of a multi-epitope vaccine targeting neonatal rotavirus with focus on outer capsid proteins VP4 and VP7 and non structural proteins NSP2 and NSP5.Scientific reports · 2025Article
- Differential Adjuvant Activity by Flagellins fromVaccines · 2024Article
- Integrating immunoinformatics and computational epitope prediction for a vaccine candidate against respiratory syncytial virus.Infectious Disease Modelling · 2024Article
- Mucosal TLR5 activation controls healthspan and longevity.Nature communications · 2024Article
- A flagellin-conjugate protein induces dual NLRC4- and NLRP3-inflammasome activation which modulates inflammatory cytokine secretion from macrophages.Frontiers in immunology · 2023Article
- Protein sociology of ProA, Mip and other secreted virulence factors at theFrontiers in cellular and infection microbiology · 2023Review
- Legionella pneumophila PPIase Mip Interacts with the Bacterial Proteins SspB, Lpc2061, and FlaA and Promotes Flagellation.Infection and immunity · 2022Article
- Article
- Design of a multi-epitope vaccine against the pathogenic fungi Candida tropicalis using an in silico approach.Journal, genetic engineering & biotechnology · 2022Article
- N-terminus of flagellin enhances vaccine efficacy against Actinobacillus pleuropneumoniae.BMC veterinary research · 2022Article
- Evolution of Phage Tail Sheath Protein.Viruses · 2022Article
- Zinc Metalloprotease ProA fromBiomolecules · 2022Article
- Immunoinformatics Aided Design andFrontiers in immunology · 2022Article
- Review
- Review
- Genetic Variation in Toll-Like Receptor 5 and Colonization with Flagellated Bacterial Vaginosis-Associated Bacteria.Infection and immunity · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Flagellin is a wide-spread bacterial virulence factor sensed by the membrane-bound Toll-like receptor 5 (TLR5) and by the intracellular NAIP5/NLRC4 inflammasome receptor. TLR5 recognizes a conserved region within the D1 domain of flagellin, crucial for the interaction between subunits in the flagellum and for bacterial motility. While it is known that a deletion of the D0 domain of flagellin, which lines the interior of flagella, also completely abrogates activation of TLR5, its functional role remains unknown. Using a protein fusion strategy, we propose a role for the D0 domain in the stabilization of an active dimeric signaling complex of flagellin-TLR5 at a 2:2 stoichiometric ratio. Alanine-scanning mutagenesis of flagellin revealed a previously unidentified region of flagellin, the C-terminal D0 domain, to play a crucial role in TLR5 activation. Interestingly, we show that TLR5 recognizes the same hydrophobic motif of the D0 domain of flagellin as the intracellular NAIP5/NLRC4 inflammasome receptor. Further, we show that residues within the D0 domain play a previously unrecognized role in the evasion of TLR5 recognition by Helicobacter pylori. These findings demonstrate that TLR5 is able to simultaneously sense several spatially separated sites of flagellin that are essential for its functionality, hindering bacterial evasion of immune recognition. Our findings significantly contribute to the understanding of the mechanism of TLR5 activation, which plays an important role in host defense against several pathogens, but also in several diseases, such as Crohn's disease, cystic fibrosis and rheumatoid arthritis.
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