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Publication Abstract from PubMed

Signaling through innate immune receptors such as the Toll-like receptor (TLR)/interleukin-1 receptor (IL-1R) superfamily proceeds via the assembly of large membrane-proximal complexes or "signalosomes." Although structurally distinct, the IL-17 receptor family triggers cellular responses that are typical of innate immune receptors. The IL-17RA receptor subunit is shared by several members of the IL-17 family. Using a combination of crystallographic, biophysical, and mutational studies, we show that IL-17A, IL-17F, and IL-17A/F induce IL-17RA dimerization. X-ray analysis of the heteromeric IL-17A complex with the extracellular domains of the IL-17RA and IL-17RC receptors reveals that cytokine-induced IL-17RA dimerization leads to the formation of a 2:2:2 hexameric signaling assembly. Furthermore, we demonstrate that the formation of the IL-17 signalosome potentiates IL-17-induced IL-36gamma and CXCL1 mRNA expression in human keratinocytes, compared with a dimerization-defective IL-17RA variant.

IL-17-induced dimerization of IL-17RA drives the formation of the IL-17 signalosome to potentiate signaling.,Goepfert A, Barske C, Lehmann S, Wirth E, Willemsen J, Gudjonsson JE, Ward NL, Sarkar MK, Hemmig R, Kolbinger F, Rondeau JM Cell Rep. 2022 Oct 18;41(3):111489. doi: 10.1016/j.celrep.2022.111489. PMID:36260993^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.