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Updated: Jul 24, 2025
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Activation and Measurement of NLRP3 Inflammasome Activity Using IL-1β in Human Monocyte-derived Dendritic Cells
Published on: May 22, 2014
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Structural basis for flagellin induced NAIP5 activation
Bhaskar Paidimuddala1, Jianhao Cao1, Liman Zhang1
1Department of Chemical Physiology and Biochemistry, Oregon Health and Science University, Portland, OR 97239, USA.
Biorxiv : the Preprint Server for Biology
|July 3, 2023
Summary
The NAIP/NLRC4 inflammasome activates via a "trap and lock" mechanism where NAIP5 binds bacterial flagellin (FliC). This binding induces conformational changes in NAIP5, initiating NLRC4 inflammasome activation.
Area of Science:
- Innate immunity
- Inflammasome biology
- Structural biology
Background:
- The NAIP/NLRC4 inflammasome is crucial for detecting gram-negative bacteria.
- NAIP activation by bacterial ligands initiates downstream immune signaling.
- The precise mechanism of NAIP conformational change upon ligand binding remains unclear.
Approach:
- Investigated the dynamics of the ligand-binding region of inactive NAIP5.
- Determined the cryo-electron microscopy (cryo-EM) structure of NAIP5 bound to FliC at 2.93 Å resolution.
Key Points:
- Revealed a "trap and lock" mechanism for FliC recognition by NAIP5.
- FliC-D0C is trapped in a hydrophobic pocket, then locked by NAIP5's insertion domain (ID) and C-terminal tail (CTT).
- FliC-D0N stabilizes the complex by inserting into the ID loop, promoting NAIP5 activation.
Conclusions:
- FliC binding induces conformational changes in NAIP5 by assembling flexible domains (ID, HD2, LRR).
- This conformational change stabilizes the WHD loop, enabling NLRC4 inflammasome activation.
- Elucidates a key step in bacterial pathogen recognition by the innate immune system.
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