The structure and binding mode of interleukin-18

Nat Struct Biol. 2003 Nov;10(11):966-71. doi: 10.1038/nsb993. Epub 2003 Oct 5.


Interleukin-18 (IL-18), a cytokine formerly known as interferon-gamma- (IFN-gamma-) inducing factor, has pleiotropic immunoregulatory functions, including augmentation of IFN-gamma production, Fas-mediated cytotoxicity and developmental regulation of T-lymphocyte helper type I. We determined the solution structure of IL-18 as a first step toward understanding its receptor activation mechanism. It folds into a beta-trefoil structure that resembles that of IL-1. Extensive mutagenesis revealed the presence of three sites that are important for receptor activation: two serve as binding sites for IL-18 receptor alpha (IL-18Ralpha), located at positions similar to those of IL-1 for IL-1 receptor type I (IL-1RI), whereas the third site may be involved in IL-18 receptor beta (IL-18Rbeta) binding. The structure and mutagenesis data provide a basis for understanding the IL-18-induced heterodimerization of receptor subunits, which is necessary for receptor activation.

MeSH terms

  • Amino Acid Sequence
  • Binding Sites
  • Humans
  • Interleukin-18 / chemistry*
  • Interleukin-18 / metabolism*
  • Interleukin-18 Receptor alpha Subunit
  • Molecular Sequence Data
  • Receptors, Interleukin / metabolism
  • Receptors, Interleukin-18


  • IL18R1 protein, human
  • Interleukin-18
  • Interleukin-18 Receptor alpha Subunit
  • Receptors, Interleukin
  • Receptors, Interleukin-18

Associated data

  • PDB/1ITB
  • PDB/1JOS
  • PDB/2I1B