| Structural highlights
4nux is a 1 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Resources: | FirstGlance, OCA, RCSB, PDBsum |
Disease
[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.[1]
Function
[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.[2] [3]
Publication Abstract from PubMed
Interleukin 17 (IL-17) cytokines play a crucial role in mediating inflammatory and autoimmune diseases. A unique intracellular signaling domain termed SEFIR is found within all IL-17 receptors (IL-17Rs) as well as the key adaptor protein Act1. SEFIR-mediated protein-protein interaction is a crucial step in IL-17 cytokine signaling. Here, the 2.3 A resolution crystal structure of the SEFIR domain of IL-17RA, the most commonly shared receptor for IL-17 cytokine signaling, is reported. The structure includes the complete SEFIR domain and an additional alpha-helical C-terminal extension, which pack tightly together to form a compact unit. Structural comparison between the SEFIR domains of IL-17RA and IL-17RB reveals substantial differences in protein topology and folding. The uniquely long insertion between strand betaC and helix alphaC in IL-17RA SEFIR is mostly well ordered, displaying a helix (alphaCC'ins) and a flexible loop (CC'). The DD' loop in the IL-17RA SEFIR structure is much shorter; it rotates nearly 90 degrees with respect to the counterpart in the IL-17RB SEFIR structure and shifts about 12 A to accommodate the alphaCC'ins helix without forming any knots. Helix alphaC was identified as critical for its interaction with Act1 and IL-17-stimulated gene expression. The data suggest that the heterotypic SEFIR-SEFIR association via helix alphaC is a conserved and signature mechanism specific for IL-17 signaling. The structure also suggests that the downstream motif of IL-17RA SEFIR together with helix alphaC could provide a composite ligand-binding surface for recruiting Act1 during IL-17 signaling.
Structure of the unique SEFIR domain from human interleukin 17 receptor A reveals a composite ligand-binding site containing a conserved alpha-helix for Act1 binding and IL-17 signaling.,Zhang B, Liu C, Qian W, Han Y, Li X, Deng J Acta Crystallogr D Biol Crystallogr. 2014 May;70(Pt 5):1476-83. doi:, 10.1107/S1399004714005227. Epub 2014 Apr 30. PMID:24816115[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
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
- ↑ 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
- ↑ Zhang B, Liu C, Qian W, Han Y, Li X, Deng J. Structure of the unique SEFIR domain from human interleukin 17 receptor A reveals a composite ligand-binding site containing a conserved alpha-helix for Act1 binding and IL-17 signaling. Acta Crystallogr D Biol Crystallogr. 2014 May;70(Pt 5):1476-83. doi:, 10.1107/S1399004714005227. Epub 2014 Apr 30. PMID:24816115 doi:http://dx.doi.org/10.1107/S1399004714005227
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