Structural basis of receptor sharing by interleukin 17 cytokines
Open accessAbstract
Interleukin 17 (IL-17)-producing helper T cells (T(H)-17 cells), together with their effector cytokines, including members of the IL-17 family, are emerging as key mediators of chronic inflammatory and autoimmune disorders. Here we present the crystal structure of a complex of IL-17 receptor A (IL-17RA) bound to IL-17F in a 1:2 stoichiometry. The mechanism of complex formation was unique for cytokines and involved the engagement of IL-17 by two fibronectin-type domains of IL-17RA in a groove between the IL-17 homodimer interface. Binding of the first receptor to the IL-17 cytokines modulated the affinity and specificity of the second receptor-binding event, thereby promoting heterodimeric versus homodimeric complex formation. IL-17RA used a common recognition strategy to bind to several members of the IL-17 family, which allows it to potentially act as a shared receptor in multiple different signaling complexes.
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IL-17A signaling is mediated through IL-17 receptor A (IL-17RA) and IL-17RC.
“IL-17A signaling is mediated through IL-17 receptor A (IL-17RA) and IL-17RC,74,75”
From The Innate Immune System in Acute and Chronic Wounds (2016) · cites this paper as [74]
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- Authors
- Ely, L. K., Fischer, S., & Garcia, K. C.
- Affiliations
- Howard Hughes Medical Institute (US)
- ORCID
- Ely, Lauren K
- Venue
- Nature Immunology
- Published
- 2009-10-18
- Volume
- 10
- Issue
- 12
- Pages
- 1245-1251
- ISSN
- 1529-2908 (ISSN-L)
- 1529-2916
- PMC
- PMC2783927
- OpenAlex
- W2166087321
- Cited by
- 195
- References
- 48
- Citations by year
- 2026: 9 · 2025: 9 · 2024: 3 · 2023: 5 · 2022: 12 · 2021: 14 · 2020: 10 · 2019: 9 · 2018: 4 · 2017: 16 · 2016: 13 · 2015: 17 · 2014: 11 · 2013: 15 · 2012: 19
- FWCI
- 7.99
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Immunology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institute of Allergy and Infectious Diseases (AI 51321, R37AI051321, R01AI051321)
- Topics
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Keywords
- IL-17, IL-17RA, IL-17F, cytokine-receptor complex, crystal structure, Th17 cells, receptor specificity, cytokine signaling
- MeSH terms
- Amino Acid Sequence, Cell Line, Humans, Models, Molecular, Molecular Sequence Data, Sequence Alignment, Conserved Sequence, Protein Structure, Tertiary, Crystallography, X-Ray, Interleukin-17, Protein Structure, Quaternary, Receptors, Interleukin-17, Protein Multimerization
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