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High resolution crystal structure of murine IL-1F5 reveals unique loop conformation for specificityHigh resolution crystal structure of murine IL-1F5 reveals unique loop conformation for specificity
Structural highlights
Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedInterleukin-1 (IL-1) F5 is a novel member of the IL-1 family. The IL-1 family are involved in innate immune responses to infection and injury. These cytokines bind to specific receptors and cause activation of NFkappaB and MAP kinase. IL-1F5 has a sequence identity of 44% to IL-1 receptor antagonist (IL-1Ra), a natural antagonist of the IL-1 system. Here we report the crystal structure of IL-1F5 to a resolution of 1.6 A. It has the same beta-trefoil fold as other IL-1 family members, and the hydrophobic core is well conserved. However, there are substantial differences in the loop conformations, structures that confer binding specificity for the cognate receptor to IL-1beta and the antagonist IL-1Ra. Docking and superimposition of the IL-1F5 structure suggest that is unlikely to bind to the interleukin1 receptor, consistent with biochemical studies. The structure IL-1F5 lacks features that confer antagonist properties on IL-1Ra, and we predict that like IL-1beta it will act as an agonist. These studies give insights into how distinct receptor specificities can evolve within related cytokine families. High-resolution structure of murine interleukin 1 homologue IL-1F5 reveals unique loop conformations for receptor binding specificity.,Dunn EF, Gay NJ, Bristow AF, Gearing DP, O'Neill LA, Pei XY Biochemistry. 2003 Sep 23;42(37):10938-44. PMID:12974628[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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