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A conserved surface on Toll-like receptor 5 recognizes bacterial flagellin
Erica Andersen-Nissen1, Kelly D Smith, Richard Bonneau
1Institute for Systems Biology, Seattle, WA 98103, USA.
Toll-like receptor 5 (TLR5) recognizes bacterial flagellins. Researchers mapped the flagellin recognition site on TLR5, identifying key residues responsible for discriminating between different flagellins and enabling TLR activation.
Area of Science:
- Immunology
- Molecular Biology
- Structural Biology
Background:
- The molecular mechanisms underlying Toll-like receptor (TLR) ligand recognition remain largely unelucidated.
- Toll-like receptor 5 (TLR5) is crucial for detecting bacterial flagellins, a key component of microbial ligands.
Purpose of the Study:
- To determine the molecular basis of flagellin recognition by TLR5.
- To map the specific region on TLR5 responsible for discriminating between different flagellin molecules.
Main Methods:
- Utilized comparative analysis of mouse and human TLR5 function.
- Employed molecular modeling of the TLR5 ectodomain.
- Conducted site-directed mutagenesis studies on conserved residues.
Main Results:
- Identified a 228-amino acid region within the TLR5 extracellular domain critical for flagellin recognition.
- Discovered that variation at TLR5 residue 268 underlies species-specific flagellin discrimination.
- Pinpointed residues D295 and D367 within a conserved surface as essential for flagellin binding and subsequent TLR activation.
Conclusions:
- Flagellin recognition by TLR5 is localized to a specific conserved surface on its extracellular domain.
- Ligand binding to beta sheets within this region initiates TLR activation.
- These findings provide a structural framework for understanding TLR-ligand interactions and TLR activation pathways.
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