6HGO

Crystal Structure of human IL-17F

Summary for 6HGO

• Entry DOI: 10.2210/pdb6hgo/pdb
• Related: 6HG4 6HG9 6HGA
• Descriptor: Interleukin-17F, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (5 entities in total)
• Functional Keywords: cystine-knot, cytokine, immune system
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 4
• Total formula weight: 63967.67

Authors

Rondeau, J.M.,Goepfert, A. (deposition date: 2018-08-23, release date: 2019-11-20, Last modification date: 2024-10-16)

Primary citation

Goepfert, A.,Lehmann, S.,Blank, J.,Kolbinger, F.,Rondeau, J.M.
Structural Analysis Reveals that the Cytokine IL-17F Forms a Homodimeric Complex with Receptor IL-17RC to Drive IL-17RA-Independent Signaling.
Immunity, 52:499-512.e5, 2020

PubMed Abstract: Interleukin-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.

PubMed: 32187518
DOI: 10.1016/j.immuni.2020.02.004

Experimental method

X-RAY DIFFRACTION (2.1 Å)