Crystal structure of the type-I interleukin-1 receptor complexed with interleukin-1beta

Nature. 1997 Mar 13;386(6621):190-4. doi: 10.1038/386190a0.


Interleukin-1 (IL-1) is an important mediator of inflammatory disease. The IL-1 family currently consists of two agonists, IL-1alpha and IL-1beta, and one antagonist, IL-1ra. Each of these molecules binds to the type I IL-1 receptor (IL1R). The binding of IL-1alpha or IL-1beta to IL1R is an early step in IL-1 signal transduction and blocking this interaction may therefore be a useful target for the development of new drugs. Here we report the three-dimensional structure of IL-1beta bound to the extracellular domain of IL1R (s-IL1R) at 2.5 A resolution. IL-1beta binds to s-IL1R with a 1:1 stoichiometry. The crystal structure shows that s-IL1R consists of three immunoglobulin-like domains which wrap around IL-1beta in a manner distinct from the structures of previously described cytokine-receptor complexes. The two receptor-binding regions on IL-1beta identified by site-directed mutagenesis both contact the receptor: one binds to the first two domains of the receptor, while the other binds exclusively to the third domain.

MeSH terms

  • Cloning, Molecular
  • Crystallography, X-Ray
  • Humans
  • Interleukin-1 / chemistry*
  • Interleukin-1 / genetics
  • Interleukin-1 / metabolism
  • Models, Molecular
  • Mutagenesis, Site-Directed
  • Protein Binding
  • Protein Conformation*
  • Receptors, Interleukin-1 / chemistry*
  • Receptors, Interleukin-1 / genetics
  • Receptors, Interleukin-1 / metabolism
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism


  • Interleukin-1
  • Receptors, Interleukin-1
  • Recombinant Proteins