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 <ref name="Jin">PMID:25168428</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 <ref name="Jin">PMID:25168428</ref>, inflammatory bowel disease <ref name="Andoh">PMID:19535621</ref><ref name="Fonseca-Camarillo">PMID:24527982</ref>, and also with host defense during bacterial infection <ref name="Ma">PMID:19830736</ref>[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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9. Goldenzweig A, Goldsmith M, Hill SE, Gertman O, Laurino P, Ashani Y, Dym O, Unger T, Albeck S, Prilusky J, Lieberman RL, Aharoni A, Silman I, Sussman JL, Tawfik DS & Fleishman SJ (2016) Automated Structure- and Sequence-Based Design of Proteins for High Bacterial Expression and Stability, Mol Cell 63, 337-346. | 9. Goldenzweig A, Goldsmith M, Hill SE, Gertman O, Laurino P, Ashani Y, Dym O, Unger T, Albeck S, Prilusky J, Lieberman RL, Aharoni A, Silman I, Sussman JL, Tawfik DS & Fleishman SJ (2016) Automated Structure- and Sequence-Based Design of Proteins for High Bacterial Expression and Stability, Mol Cell 63, 337-346. | ||
Revision as of 12:14, 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.
