6DF3

Crystal structure of ternary complex of IL-24 with soluble receptors IL-22RA and IL-20RB

6DF3 の概要

• エントリーDOI: 10.2210/pdb6df3/pdb
• 分子名称: Interleukin-22 receptor subunit alpha-1, Interleukin-24, Interleukin-20 receptor subunit beta, ... (7 entities in total)
• 機能のキーワード: cytokine, ternary complex, cell signaling, jak-stat pathway
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 63957.79

構造登録者

Lubkowski, J.,Wlodawer, A. (登録日: 2018-05-14, 公開日: 2018-08-15, 最終更新日: 2024-10-30)

主引用文献

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

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: 30111632
DOI: 10.4049/jimmunol.1800726

実験手法

X-RAY DIFFRACTION (2.15 Å)