Cutting edge: identification of a pre-ligand assembly domain (PLAD) and ligand binding site in the IL-17 receptor

J Immunol. 2007 Nov 15;179(10):6379-83. doi: 10.4049/jimmunol.179.10.6379.


IL-17 is the hallmark cytokine of the newly described "Th17" lymphocyte population. The composition, subunit dynamics, and ligand contacts of the IL-17 receptor are poorly defined. We previously demonstrated that the IL-17RA subunit oligomerizes in the membrane without a ligand. In this study, computational modeling identified two fibronectin-III-like (FN) domains in IL-17RA connected by a nonstructured linker, which we predicted to mediate homotypic interactions. In yeast two-hybrid, the membrane-proximal FN domain (FN2), but not the membrane-distal domain (FN1), formed homomeric interactions. The ability of FN2 to drive ligand-independent multimerization was verified by coimmunoprecipitation and fluorescence resonance energy transfer microscopy. Thus, FN2 constitutes a "pre-ligand assembly domain" (PLAD). Further studies indicated that the FN2 linker domain contains the IL-17 binding site, which was never mapped. However, the FN1 domain is also required for high affinity interactions with IL-17. Therefore, although the PLAD is located entirely within FN2, effective ligand binding also involves contributions from the linker and FN1.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Binding Sites / genetics
  • Binding Sites / immunology
  • Cell Line
  • Fluorescence Resonance Energy Transfer
  • Humans
  • Interleukin-17 / immunology
  • Interleukin-17 / metabolism
  • Ligands
  • Lymphocytes / immunology
  • Lymphocytes / metabolism
  • Models, Molecular*
  • Peptide Mapping
  • Protein Binding / genetics
  • Protein Binding / immunology
  • Protein Structure, Quaternary / genetics
  • Protein Structure, Tertiary / genetics
  • Receptors, Interleukin-17 / genetics*
  • Receptors, Interleukin-17 / immunology
  • Receptors, Interleukin-17 / metabolism
  • Two-Hybrid System Techniques


  • IL17RA protein, human
  • Interleukin-17
  • Ligands
  • Receptors, Interleukin-17