| Structural highlights
Disease
[IL17F_HUMAN] Defects in IL17F are the cause of familial candidiasis type 6 (CANDF6) [MIM:613956]. CANDF6 is a rare disorder with altered immune responses and impaired clearance of fungal infections, selective against Candida. It is characterized by persistent and/or recurrent infections of the skin, nails and mucous membranes caused by organisms of the genus Candida, mainly Candida albicans.[1] [I17RA_HUMAN] Defects in IL17RA are the cause of familial candidiasis type 5 (CANDF5) [MIM:613953]. CANDF5 is a rare disorder with altered immune responses and impaired clearance of fungal infections, selective against Candida. It is characterized by persistent and/or recurrent infections of the skin, nails and mucous membranes caused by organisms of the genus Candida, mainly Candida albicans.[2]
Function
[IL17F_HUMAN] Stimulates the production of other cytokines such as IL-6, IL-8 and granulocyte colony-stimulating factor, and can regulate cartilage matrix turnover. Stimulates PBMC and T-cell proliferation. Inhibits angiogenesis. [I17RA_HUMAN] Receptor for IL17A, IL17F and, in dimer with IL17RE, for IL17C. Binds its IL17A ligand with low affinity, suggesting that additional components are involved in IL17A-induced signaling.[3] [4]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
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.
Structural basis of receptor sharing by interleukin 17 cytokines.,Ely LK, Fischer S, Garcia KC Nat Immunol. 2009 Dec;10(12):1245-51. Epub 2009 Oct 18. PMID:19838198[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Puel A, Cypowyj S, Bustamante J, Wright JF, Liu L, Lim HK, Migaud M, Israel L, Chrabieh M, Audry M, Gumbleton M, Toulon A, Bodemer C, El-Baghdadi J, Whitters M, Paradis T, Brooks J, Collins M, Wolfman NM, Al-Muhsen S, Galicchio M, Abel L, Picard C, Casanova JL. Chronic mucocutaneous candidiasis in humans with inborn errors of interleukin-17 immunity. Science. 2011 Apr 1;332(6025):65-8. doi: 10.1126/science.1200439. Epub 2011 Feb, 24. PMID:21350122 doi:10.1126/science.1200439
- ↑ Puel A, Cypowyj S, Bustamante J, Wright JF, Liu L, Lim HK, Migaud M, Israel L, Chrabieh M, Audry M, Gumbleton M, Toulon A, Bodemer C, El-Baghdadi J, Whitters M, Paradis T, Brooks J, Collins M, Wolfman NM, Al-Muhsen S, Galicchio M, Abel L, Picard C, Casanova JL. Chronic mucocutaneous candidiasis in humans with inborn errors of interleukin-17 immunity. Science. 2011 Apr 1;332(6025):65-8. doi: 10.1126/science.1200439. Epub 2011 Feb, 24. PMID:21350122 doi:10.1126/science.1200439
- ↑ Ramirez-Carrozzi V, Sambandam A, Luis E, Lin Z, Jeet S, Lesch J, Hackney J, Kim J, Zhou M, Lai J, Modrusan Z, Sai T, Lee W, Xu M, Caplazi P, Diehl L, de Voss J, Balazs M, Gonzalez L Jr, Singh H, Ouyang W, Pappu R. IL-17C regulates the innate immune function of epithelial cells in an autocrine manner. Nat Immunol. 2011 Oct 12;12(12):1159-66. doi: 10.1038/ni.2156. PMID:21993848 doi:10.1038/ni.2156
- ↑ Ely LK, Fischer S, Garcia KC. Structural basis of receptor sharing by interleukin 17 cytokines. Nat Immunol. 2009 Dec;10(12):1245-51. Epub 2009 Oct 18. PMID:19838198 doi:10.1038/ni.1813
- ↑ Ely LK, Fischer S, Garcia KC. Structural basis of receptor sharing by interleukin 17 cytokines. Nat Immunol. 2009 Dec;10(12):1245-51. Epub 2009 Oct 18. PMID:19838198 doi:10.1038/ni.1813
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