Crystal Structure of the Labile Complex of IL-24 with the Extracellular Domains of IL-22R1 and IL-20R2
| العنوان: | Crystal Structure of the Labile Complex of IL-24 with the Extracellular Domains of IL-22R1 and IL-20R2 |
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| المؤلفون: | Jacek Lubkowski, Andriy Anishkin, Alexander Wlodawer, Cem Sonmez, Sergei V. Kotenko, Sergey V. Smirnov |
| المصدر: | The Journal of Immunology. 201:2082-2093 |
| بيانات النشر: | The American Association of Immunologists, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | 0301 basic medicine, Protein Conformation, Immunology, Plasma protein binding, Crystallography, X-Ray, Article, Cell Line, 03 medical and health sciences, 0302 clinical medicine, Protein structure, Protein Domains, Animals, Humans, Immunology and Allergy, Receptor, Ternary complex, Schneider 2 cells, Chemistry, Interleukins, Receptors, Interleukin, Ligand (biochemistry), 030104 developmental biology, Multiprotein Complexes, 030220 oncology & carcinogenesis, Biophysics, Cytokines, Drosophila, Signal transduction, Protein Binding, Signal Transduction, Cysteine |
| الوصف: | 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. |
| تدمد: | 1550-6606 0022-1767 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e8fa097b0d4504e21e04988fe7b10b39Test https://doi.org/10.4049/jimmunol.1800726Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....e8fa097b0d4504e21e04988fe7b10b39 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15506606 00221767 |
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