Structural basis for the specific recognition of IL-18 by its alpha receptor

FEBS Lett. 2014 Nov 3;588(21):3838-43. doi: 10.1016/j.febslet.2014.09.019. Epub 2014 Sep 26.

Abstract

Interleukin 18 (IL-18), a member of the IL-1 family of cytokines, is an important regulator of innate and acquired immune responses. It signals through its ligand-binding primary receptor IL-18Rα and accessory receptor IL-18Rβ. Here we report the crystal structure of IL-18 with the ectodomain of IL-18Rα, which reveals the structural basis for their specific recognition. It confirms that surface charge complementarity determines the ligand-binding specificity of primary receptors in the IL-1 receptor family. We suggest that IL-18 signaling complex adopts an architecture similar to other agonistic cytokines and propose a general ligand-receptor assembly and activation model for the IL-1 family.

Keywords: Interleukin 18; Interleukin 18 receptor; Ligand-receptor recognition; X-ray structure.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Crystallography, X-Ray
  • Humans
  • Interleukin-1 / metabolism
  • Interleukin-18 / chemistry*
  • Interleukin-18 / metabolism*
  • Interleukin-18 Receptor alpha Subunit / chemistry*
  • Interleukin-18 Receptor alpha Subunit / metabolism*
  • Ligands
  • Models, Molecular
  • Protein Binding
  • Protein Structure, Tertiary
  • Sf9 Cells
  • Spodoptera
  • Substrate Specificity
  • Surface Properties

Substances

  • Interleukin-1
  • Interleukin-18
  • Interleukin-18 Receptor alpha Subunit
  • Ligands