6DF3
Crystal structure of ternary complex of IL-24 with soluble receptors IL-22RA and IL-20RB
Summary for 6DF3
| Entry DOI | 10.2210/pdb6df3/pdb |
| Descriptor | Interleukin-22 receptor subunit alpha-1, Interleukin-24, Interleukin-20 receptor subunit beta, ... (7 entities in total) |
| Functional Keywords | cytokine, ternary complex, cell signaling, jak-stat pathway |
| Biological source | Homo sapiens (Human) More |
| Total number of polymer chains | 3 |
| Total formula weight | 63957.79 |
| Authors | Lubkowski, J.,Wlodawer, A. (deposition date: 2018-05-14, release date: 2018-08-15, Last modification date: 2024-10-30) |
| Primary citation | Lubkowski, J.,Sonmez, C.,Smirnov, S.V.,Anishkin, A.,Kotenko, S.V.,Wlodawer, A. Crystal Structure of the Labile Complex of IL-24 with the Extracellular Domains of IL-22R1 and IL-20R2. J. Immunol., 201:2082-2093, 2018 Cited by PubMed Abstract: 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 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 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. PubMed: 30111632DOI: 10.4049/jimmunol.1800726 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.15 Å) |
Structure validation
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