ArticleBiology direct2017
Integrative modelling of TIR domain-containing adaptor molecule inducing interferon-β (TRIF) provides insights into its autoinhibited state.
Article in Biology direct, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.
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Who cites it
10 citing papers in PubMed, 1 synthesis or guideline pooled it, 14 citations in OpenAlex.
- TIR domain proteins: regulatory mechanisms in the tumor immune microenvironment, clinical translation strategies, and prospects for precision therapy applications.Frontiers in immunology · 2025Pooled it
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- Toll-like receptor 4 pathway evolutionary trajectory and functional emergence.Frontiers in immunology · 2024Article
- Review
- Contribution of the mutation rs8193069 in TLR4 to mastitis resistance and performance in Holstein cows in southern China.Veterinary medicine and science · 2022Article
- Heterologous Expression and Assembly of Human TLR Signaling Components inBiomolecules · 2021Article
- Toll-like receptor 3 (TLR3) regulation mechanisms and roles in antiviral innate immune responses.Journal of Zhejiang University. Science. B · 2021Review
- The SARS-Cov-2 Proliferation Blocked by a Novel and Potent Main Protease Inhibitor via Computer-aided Drug Design.Iranian journal of pharmaceutical research : IJPR · 2021Article
- SCRIBER: accurate and partner type-specific prediction of protein-binding residues from proteins sequences.Bioinformatics (Oxford, England) · 2019Article
- Viruses Seen by Our Cells: The Role of Viral RNA Sensors.Journal of immunology research · 2018Review
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2 authors at 1 institution in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
backgroundTRIF is a key protein in antiviral innate immunity, operating downstream of TLRs. TRIF activation leads to the production of interferon-β and pro-inflammatory cytokines. There is evidence from experiments to suggest that the N-terminal domain of TRIF binds to its TIR domain to avoid constitutive activation. However, no structure of a complex between the N-terminal domain and the TIR domain exists till date. The disordered nature of the region connecting the N-terminal domain and the TIR domain compounds the issue of elucidating the mechanism of autoinhibition of TRIF. In this study, we have employed an integrative approach consisting of mutual information analysis, docking, molecular dynamics simulations and residue network analysis, in combination with existing experimental data to provide a glimpse of TRIF in its autoinhibited state.
resultsOur extensive docking approach reveals that the N-terminal domain binds to the BB loop-B helix region of the TIR domain, consistent with experimental observations. Long length molecular dynamics simulations of 1 microsecond performed on the docked model highlights residues participating in hydrogen bonding and hydrophobic interactions at the interface. A pair of residues present in the vicinity of the interface is also predicted by mutual information analysis, to co-evolve. Residues mediating long-range interactions within the TIR domain of TRIF were identified using residue network analysis.
conclusionsBased on the results of the modelling and residue network analysis, we propose that the N-terminal domain binds to the BB loop region of the TIR domain, thereby preventing its homodimersation. The binding of TRIF to TLR3 or TRAM could induce a slight conformational change, causing the interactions between the N-terminal domain and TIR domain to disrupt, thereby exposing the BB loop and rendering it amenable for higher-order oligomerisation. REVIEWERS: This article was reviewed by Michael Gromiha, Srikrishna Subramaniam and Peter Bond (nominated by Chandra Verma).
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