Journal:FEBS Journal:1
From Proteopedia
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<b>Molecular Tour</b><br> | <b>Molecular Tour</b><br> | ||
Interleukin 24 (IL-24) is cytokine, member of Interleukin 10 family. It forms an IL-20 subfamily with IL-19, IL-20, IL-22 because all these interleukins use the common class II cytokine receptor subunits and have similarities in biological functions <ref name="Rutz">PMID:25421700</ref>. IL-24 signals via two heterodimeric receptor complexes IL-22R1/IL-20R2 and IL-20R1/IL-20R2 and activates the STAT3 and STAT1 signaling (fig.1) <ref name="Dumoutier">PMID:11564763</ref><ref name="Wang">PMID:15667561</ref>. | Interleukin 24 (IL-24) is cytokine, member of Interleukin 10 family. It forms an IL-20 subfamily with IL-19, IL-20, IL-22 because all these interleukins use the common class II cytokine receptor subunits and have similarities in biological functions <ref name="Rutz">PMID:25421700</ref>. IL-24 signals via two heterodimeric receptor complexes IL-22R1/IL-20R2 and IL-20R1/IL-20R2 and activates the STAT3 and STAT1 signaling (fig.1) <ref name="Dumoutier">PMID:11564763</ref><ref name="Wang">PMID:15667561</ref>. | ||
| - | IL-24 is associated with multiple diseases, including the promotion and amplification of inflammatory responses during autoimmune and chronic inflammation <ref name="Rutz">PMID:25421700</ref>, psoriasis-like skin inflammation <ref name="Kumari">PMID:24211183</ref>, epidermal inflammation induced by stresses [5], inflammatory bowel disease | + | IL-24 is associated with multiple diseases, including the promotion and amplification of inflammatory responses during autoimmune and chronic inflammation <ref name="Rutz">PMID:25421700</ref>, psoriasis-like skin inflammation <ref name="Kumari">PMID:24211183</ref>, epidermal inflammation induced by stresses <ref name="Jin">PMID:25168428</ref>[5], inflammatory bowel disease <ref name="Andoh">PMID:19535621</ref><ref name="Fonseca-Camarillo">PMID:24527982</ref>, and also with host defense during bacterial infection [8]. Some studies suggest anti-cancer activities that increased the interest in this molecule. |
One of the stable variants (IL-24B) was crystallized, its structure solved at 1.3 Å resolution and deposited to PDB under the code 6gg1. This structure together with the recently published crystal structure of the ternary complex of IL-24 fused to IL-22R1 and co-expressed with IL-20R2 (PDB ID [[6df3]], [13]) allowed us to analyze the role of the mutated amino acid residues protein stability, flexibility, and binding to the cognate receptors (fig.2). Based on the analysis, we expressed a series of variants back engineered from the PROSS designed variant by changing the critical residues back to their wild types. We revealed that re-introduction of a single IL-24 wild type residue (T198) to the patch interacting with receptors 1 restored 80 % of the binding affinity and signaling capacity accompanied by an acceptable drop in the protein stability by 9°C. | One of the stable variants (IL-24B) was crystallized, its structure solved at 1.3 Å resolution and deposited to PDB under the code 6gg1. This structure together with the recently published crystal structure of the ternary complex of IL-24 fused to IL-22R1 and co-expressed with IL-20R2 (PDB ID [[6df3]], [13]) allowed us to analyze the role of the mutated amino acid residues protein stability, flexibility, and binding to the cognate receptors (fig.2). Based on the analysis, we expressed a series of variants back engineered from the PROSS designed variant by changing the critical residues back to their wild types. We revealed that re-introduction of a single IL-24 wild type residue (T198) to the patch interacting with receptors 1 restored 80 % of the binding affinity and signaling capacity accompanied by an acceptable drop in the protein stability by 9°C. | ||
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| - | 5. Jin SH, Choi D, Chun YJ & Noh M (2014) Keratinocyte-derived IL-24 plays a role in the positive feedback regulation of epidermal inflammation in response to environmental and endogenous toxic stressors, Toxicol Appl Pharmacol 280, 199-206. | ||
| - | 6. Andoh A, Shioya M, Nishida A, Bamba S, Tsujikawa T, Kim-Mitsuyama S & Fujiyama Y (2009) Expression of IL-24, an activator of the JAK1/STAT3/SOCS3 cascade, is enhanced in inflammatory bowel disease, J Immunol 183, 687-95. | ||
| - | 7. Fonseca-Camarillo G, Furuzawa-Carballeda J, Granados J & Yamamoto-Furusho JK (2014) Expression of interleukin (IL)-19 and IL-24 in inflammatory bowel disease patients: a cross-sectional study, Clin Exp Immunol 177, 64-75. | ||
8. Ma Y, Chen H, Wang Q, Luo F, Yan J & Zhang XL (2009) IL-24 protects against Salmonella typhimurium infection by stimulating early neutrophil Th1 cytokine production, which in turn activates CD8+ T cells, Eur J Immunol 39, 3357-68. | 8. Ma Y, Chen H, Wang Q, Luo F, Yan J & Zhang XL (2009) IL-24 protects against Salmonella typhimurium infection by stimulating early neutrophil Th1 cytokine production, which in turn activates CD8+ T cells, Eur J Immunol 39, 3357-68. | ||
Revision as of 12:12, 16 June 2019
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This page complements a publication in scientific journals and is one of the Proteopedia's Interactive 3D Complement pages. For aditional details please see I3DC.
