Related Experiment Videos
The structure and binding mode of interleukin-18.
Zenichiro Kato1, JunGoo Jee, Hiroaki Shikano
1Department of Pediatrics, Gifu University School of Medicine, Tsukasa 40, Gifu 500-8705, Japan. zen-k@cc.gifu-u.ac.jp
Nature Structural Biology
|October 7, 2003
Summary
Interleukin-18 (IL-18) has a beta-trefoil structure crucial for immune responses. Mutagenesis identified key binding sites for its receptors, explaining how IL-18 activates immune cells.
Area of Science:
- Immunology and Structural Biology
Background:
- Interleukin-18 (IL-18), a cytokine with diverse immunoregulatory functions, was previously known as the interferon-gamma (IFN-gamma) inducing factor.
- IL-18 plays roles in augmenting IFN-gamma production, enhancing Fas-mediated cytotoxicity, and regulating T-lymphocyte helper type I development.
Purpose of the Study:
- To determine the solution structure of IL-18 to elucidate its receptor activation mechanism.
- To identify critical sites involved in IL-18 receptor binding and activation.
Main Methods:
- Solution structure determination of Interleukin-18 (IL-18).
- Extensive mutagenesis of IL-18 to identify functional sites.
- Structural comparison with Interleukin-1 (IL-1).
Main Results:
- IL-18 adopts a beta-trefoil fold, similar to IL-1.
- Three key sites for receptor activation were identified through mutagenesis.
- Two sites bind IL-18 receptor alpha (IL-18Ralpha), analogous to IL-1 binding IL-1 receptor I (IL-1RI); a third site likely interacts with IL-18 receptor beta (IL-18Rbeta).
Conclusions:
- The determined structure and mutagenesis data provide a mechanistic basis for understanding IL-18 receptor activation.
- IL-18-induced heterodimerization of receptor subunits, essential for signaling, is explained by the identified binding sites.