5N9B

Crystal Structure of unliganded human IL-17RA

Summary for 5N9B

• Entry DOI: 10.2210/pdb5n9b/pdb
• Related: 5N92
• Descriptor: Interleukin-17 receptor A, 2-acetamido-2-deoxy-beta-D-glucopyranose (3 entities in total)
• Functional Keywords: fibronectin type iii, signaling protein
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 34084.45

Authors

Rondeau, J.-M.,Goepfert, A. (deposition date: 2017-02-24, release date: 2018-06-13, Last modification date: 2024-01-31)

Primary citation

Goepfert, A.,Barske, C.,Lehmann, S.,Wirth, E.,Willemsen, J.,Gudjonsson, J.E.,Ward, N.L.,Sarkar, M.K.,Hemmig, R.,Kolbinger, F.,Rondeau, J.M.
IL-17-induced dimerization of IL-17RA drives the formation of the IL-17 signalosome to potentiate signaling.
Cell Rep, 41:111489-111489, 2022

PubMed Abstract: 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-36γ and CXCL1 mRNA expression in human keratinocytes, compared with a dimerization-defective IL-17RA variant.

PubMed: 36260993
DOI: 10.1016/j.celrep.2022.111489

Experimental method

X-RAY DIFFRACTION (1.9 Å)