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Journal:FEBS Journal:1

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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]]<ref name="Lub">PMID:30111632</ref>) allowed us to analyze the role of the mutated amino acid residues protein stability, flexibility, and binding to the cognate receptors. <scene name='81/818542/Cv/5'>Structure comparison of the 6gg1 (green) and 6df3 (white)</scene>. 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]]<ref name="Lub">PMID:30111632</ref>) allowed us to analyze the role of the mutated amino acid residues protein stability, flexibility, and binding to the cognate receptors. <scene name='81/818542/Cv/5'>Structure comparison of the 6gg1 (green) and 6df3 (white)</scene>. 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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Additional references: <ref name="Goldenzweig">PMID:27425410</ref><ref name="Musil">PMID:28449074</ref><ref name="Frey">PMID:24636565</ref><ref name="Gorlich">PMID:24636567</ref>
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Additional reading: <ref name="Goldenzweig">PMID:27425410</ref><ref name="Musil">PMID:28449074</ref><ref name="Frey">PMID:24636565</ref><ref name="Gorlich">PMID:24636567</ref>
<b>References</b><br>
<b>References</b><br>

Revision as of 12:36, 17 June 2019

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