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6hga
From Proteopedia
Crystal Structure of the human IL-17RC D2-D3-D4 domains in complex with an anti-APP tag Fab
Structural highlights
Disease[I17RC_HUMAN] Chronic mucocutaneous candidiasis. The disease is caused by mutations affecting the gene represented in this entry. Function[I17RC_HUMAN] Receptor for IL17A and IL17F homodimers as part of a heterodimeric complex with IL17RA (PubMed:16785495). Receptor for the heterodimer formed by IL17A and IL17B as part of a heterodimeric complex with IL17RA (PubMed:18684971). Has also been shown to be the cognate receptor for IL17F and to bind IL17A with high affinity without the need for IL17RA (PubMed:17911633). Activation of IL17RC leads to induction of expression of inflammatory chemokines and cytokines such as CXCL1 (PubMed:16785495).[1] [2] [3] Receptor for both IL17A and IL17F.[4] Does not bind IL17A or IL17F.[5] Does not bind IL17A or IL17F.[6] Receptor for both IL17A and IL17F.[7] Publication Abstract from PubMedInterleukin-17A (IL-17A), IL-17F, and IL-17A/F heterodimers are key cytokines of the innate and adaptive immune response. Dysregulation of the IL-17 pathway contributes to immune pathology, and it is therefore important to elucidate the molecular mechanisms that govern IL-17 recognition and signaling. The receptor IL-17RC is thought to act in concert with IL-17RA to transduce IL-17A-, IL-17F-, and IL-17A/F-mediated signals. We report the crystal structure of the extracellular domain of human IL-17RC in complex with IL-17F. In contrast to the expected model, we found that IL-17RC formed a symmetrical 2:1 complex with IL-17F, thus competing with IL-17RA for cytokine binding. Using biophysical techniques, we showed that IL-17A and IL-17A/F also form 2:1 complexes with IL-17RC, suggesting the possibility of IL-17RA-independent IL-17 signaling pathways. The crystal structure of the IL-17RC:IL-17F complex provides a structural basis for IL-17F signaling through IL-17RC, with potential therapeutic applications for respiratory allergy and inflammatory bowel diseases. Structural Analysis Reveals that the Cytokine IL-17F Forms a Homodimeric Complex with Receptor IL-17RC to Drive IL-17RA-Independent Signaling.,Goepfert A, Lehmann S, Blank J, Kolbinger F, Rondeau JM Immunity. 2020 Mar 17;52(3):499-512.e5. doi: 10.1016/j.immuni.2020.02.004. PMID:32187518[8] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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