Journal:FEBS Journal:1
From Proteopedia
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| - | <StructureSection load='' size='450' side='right' scene=' | + | <StructureSection load='' size='450' side='right' scene='81/818542/Cv/1' caption=''> |
===Flexible regions govern promiscuous binding of IL-24 to receptors IL-20R1 and IL-22R1=== | ===Flexible regions govern promiscuous binding of IL-24 to receptors IL-20R1 and IL-22R1=== | ||
<big>Jiří Zahradník, Lucie Kolářová, Yoav Peleg, Petr Kolenko, Silvie Svidenská, Tatsiana Charnavets, Tamar Unger, Joel L. Sussman, and Bohdan Schneider</big> <ref>REF</ref> | <big>Jiří Zahradník, Lucie Kolářová, Yoav Peleg, Petr Kolenko, Silvie Svidenská, Tatsiana Charnavets, Tamar Unger, Joel L. Sussman, and Bohdan Schneider</big> <ref>REF</ref> | ||
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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 [1]. 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) [2, 3]. | 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 [1]. 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) [2, 3]. | ||
IL-24 is associated with multiple diseases, including the promotion and amplification of inflammatory responses during autoimmune and chronic inflammation [1], psoriasis-like skin inflammation [4], epidermal inflammation induced by stresses [5], inflammatory bowel disease [6, 7], and also with host defense during bacterial infection [8]. Some studies suggest anti-cancer activities that increased the interest in this molecule. | IL-24 is associated with multiple diseases, including the promotion and amplification of inflammatory responses during autoimmune and chronic inflammation [1], psoriasis-like skin inflammation [4], epidermal inflammation induced by stresses [5], inflammatory bowel disease [6, 7], 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. |
1. Rutz S, Wang X & Ouyang W (2014) The IL-20 subfamily of cytokines--from host defence to tissue homeostasis, Nat Rev Immunol 14, 783-95. | 1. Rutz S, Wang X & Ouyang W (2014) The IL-20 subfamily of cytokines--from host defence to tissue homeostasis, Nat Rev Immunol 14, 783-95. | ||
Revision as of 11:34, 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.
