Crystal Structure of the Labile Complex of IL-24 with the Extracellular Domains of IL-22R1 and IL-20R2

J Immunol. 2018 Oct 1;201(7):2082-2093. doi: 10.4049/jimmunol.1800726. Epub 2018 Aug 15.


Crystal structure of the ternary complex of human IL-24 with two receptors, IL-22R1 and IL-20R2, has been determined at 2.15 Å resolution. A crystallizable complex was created by a novel approach involving fusing the ligand with a flexible linker to the presumed low-affinity receptor, and coexpression of this construct in Drosophila S2 cells together with the presumed high-affinity receptor. This approach, which may be generally applicable to other multiprotein complexes with low-affinity components, was necessitated by the instability of IL-24 expressed by itself in either bacteria or insect cells. Although IL-24 expressed in Escherichia coli was unstable and precipitated almost immediately upon its refolding and purification, a small fraction of IL-24 remaining in the folded state was shown to be active in a cell-based assay. In the crystal structure presented here, we found that two cysteine residues in IL-24 do not form a predicted disulfide bond. Lack of structural restraint by disulfides, present in other related cytokines, is most likely reason for the low stability of IL-24. Although the contact area between IL-24 and IL-22R1 is larger than between the cytokine and IL-20R2, calculations show the latter interaction to be slightly more stable, suggesting that the shared receptor (IL-20R2) might be the higher-affinity receptor.

Publication types

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

MeSH terms

  • Animals
  • Cell Line
  • Crystallography, X-Ray
  • Cytokines
  • Drosophila
  • Humans
  • Interleukins / metabolism*
  • Multiprotein Complexes / metabolism*
  • Protein Binding
  • Protein Conformation
  • Protein Domains / genetics
  • Receptors, Interleukin / genetics
  • Receptors, Interleukin / metabolism*
  • Signal Transduction


  • Cytokines
  • Interleukins
  • Multiprotein Complexes
  • Receptors, Interleukin
  • interleukin-20 receptor
  • interleukin-22 receptor
  • interleukin-24