Structural basis of receptor sharing by interleukin 17 cytokines

Nat Immunol. 2009 Dec;10(12):1245-51. doi: 10.1038/ni.1813. Epub 2009 Oct 18.

Abstract

Interleukin 17 (IL-17)-producing helper T cells (T(H)-17 cells), together with their effector cytokines, including members of the IL-17 family, are emerging as key mediators of chronic inflammatory and autoimmune disorders. Here we present the crystal structure of a complex of IL-17 receptor A (IL-17RA) bound to IL-17F in a 1:2 stoichiometry. The mechanism of complex formation was unique for cytokines and involved the engagement of IL-17 by two fibronectin-type domains of IL-17RA in a groove between the IL-17 homodimer interface. Binding of the first receptor to the IL-17 cytokines modulated the affinity and specificity of the second receptor-binding event, thereby promoting heterodimeric versus homodimeric complex formation. IL-17RA used a common recognition strategy to bind to several members of the IL-17 family, which allows it to potentially act as a shared receptor in multiple different signaling complexes.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Cell Line
  • Conserved Sequence
  • Crystallography, X-Ray
  • Humans
  • Interleukin-17 / chemistry*
  • Interleukin-17 / immunology
  • Interleukin-17 / metabolism*
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Multimerization*
  • Protein Structure, Quaternary
  • Protein Structure, Tertiary
  • Receptors, Interleukin-17 / chemistry*
  • Receptors, Interleukin-17 / immunology
  • Receptors, Interleukin-17 / metabolism*
  • Sequence Alignment

Substances

  • Interleukin-17
  • Receptors, Interleukin-17

Associated data

  • PDB/3JVF