Journal:FEBS Journal:1
From Proteopedia
Flexible regions govern promiscuous binding of IL-24 to receptors IL-20R1 and IL-22R1Jiří Zahradník, Lucie Kolářová, Yoav Peleg, Petr Kolenko, Silvie Svidenská, Tatsiana Charnavets, Tamar Unger, Joel L. Sussman, and Bohdan Schneider [1] Molecular Tour 
IL-24 is associated with multiple diseases, including the promotion and amplification of inflammatory responses during autoimmune and chronic inflammation [2], psoriasis-like skin inflammation [8], epidermal inflammation induced by stresses [9], inflammatory bowel disease [10][11], and also with host defense during bacterial infection [12]. 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[7]) allowed us to analyze the role of the mutated amino acid residues protein stability, flexibility, and binding to the cognate receptors. Structure comparison of the 6gg1 (green) and 6df3 (white). 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. Additional reading: [13][14][15][16] PDB reference: Structure of PROSS-edited human interleukin 24, 6gg1. References
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