Structural insights into the assembly and activation of IL-1β with its receptors

Nat Immunol. 2010 Oct;11(10):905-11. doi: 10.1038/ni.1925. Epub 2010 Aug 29.


Interleukin 1β (IL-1β) is a key orchestrator of inflammation and host defense that exerts its effects through IL-1 receptor type I (IL-1RI) and IL-1 receptor accessory protein (IL-1RAcP). How IL-1RAcP is recruited by IL-1β-IL-1RI to form the signaling-competent complex remains elusive. Here we present the crystal structure of IL-1β bound to IL-1 receptor type II (IL-1RII) and IL-1RAcP. IL-1β-IL-1RII generated a composite binding surface to recruit IL-1RAcP. Biochemical analysis demonstrated that IL-1β-IL-1RI and IL-1β-IL-1RII interacted similarly with IL-1RAcP. It also showed the importance of two loops of IL-1 receptor antagonist (IL-1Ra) in determining its antagonism. Our results provide a structural basis for assembly and activation of the IL-1 receptor and offer a general cytokine-receptor architecture that governs the IL-1 family of cytokines.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Crystallography
  • Humans
  • Interleukin 1 Receptor Antagonist Protein / chemistry
  • Interleukin-1 Receptor Accessory Protein / chemistry*
  • Interleukin-1 Receptor Accessory Protein / metabolism
  • Interleukin-1beta / chemistry*
  • Interleukin-1beta / metabolism
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Binding
  • Protein Structure, Tertiary
  • Receptors, Interleukin-1 Type II / chemistry*
  • Receptors, Interleukin-1 Type II / metabolism
  • Sequence Alignment
  • Signal Transduction


  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1 Receptor Accessory Protein
  • Interleukin-1beta
  • Receptors, Interleukin-1 Type II