5N92

Crystal Structure of Human IL-17AF

Summary for 5N92

• Entry DOI: 10.2210/pdb5n92/pdb
• Descriptor: Interleukin-17A, Interleukin-17F, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose, ... (4 entities in total)
• Functional Keywords: cystine-knot, heterodimer, immune system
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 2
• Total formula weight: 31412.56

Authors

Rondeau, J.-M.,Goepfert, A. (deposition date: 2017-02-24, release date: 2017-09-06, Last modification date: 2020-07-29)

Primary citation

Goepfert, A.,Lehmann, S.,Wirth, E.,Rondeau, J.M.
The human IL-17A/F heterodimer: a two-faced cytokine with unique receptor recognition properties.
Sci Rep, 7:8906-8906, 2017

PubMed Abstract: IL-17A and IL-17F are prominent members of the IL-17 family of cytokines that regulates both innate and adaptive immunity. IL-17A has been implicated in chronic inflammatory and autoimmune diseases, and anti-IL-17A antibodies have shown remarkable clinical efficacy in psoriasis and psoriatic arthritis patients. IL-17A and IL-17F are homodimeric cytokines that can also form the IL-17A/F heterodimer whose precise role in health and disease remains elusive. All three cytokines signal through the assembly of a ternary complex with the IL-17RA and IL-17RC receptors. Here we report the X-ray analysis of the human IL-17A/F heterodimer that reveals a two-faced cytokine closely mimicking IL-17A as well as IL-17F. We also present the crystal structure of its complex with the IL-17RA receptor. Unexpectedly in view of the much higher affinity of this receptor toward IL-17A, we find that IL-17RA is bound to the "F-face" of the heterodimer in the crystal. Using site-directed mutagenesis, we then demonstrate that IL-17RA can also bind to the "A-face" of IL-17A/F with similar affinity. Further, we show that IL-17RC does not discriminate between the two faces of the cytokine heterodimer either, thus enabling the formation of two topologically-distinct heterotrimeric complexes with potentially different signaling properties.

PubMed: 28827714
DOI: 10.1038/s41598-017-08360-9

Experimental method

X-RAY DIFFRACTION (2.3 Å)