| Structural highlights
Disease
[I10R2_HUMAN] Autosomal recessive early-onset inflammatory bowel disease. The disease is caused by mutations affecting the gene represented in this entry.
Function
[I10R2_HUMAN] Shared cell surface receptor required for the activation of five class 2 cytokines: IL10, IL22, IL26, IL28, and IFNL1. The IFNLR1/IL10RB dimer is a receptor for the cytokine ligands IFNL2 and IFNL3 and mediates their antiviral activity. The ligand/receptor complex stimulate the activation of the JAK/STAT signaling pathway leading to the expression of IFN-stimulated genes (ISG), which contribute to the antiviral state.[1] [2]
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
IL-10R2 is a shared cell surface receptor required for the activation of five class 2 cytokines (IL-10, IL-22, IL-26, IL-28, and IL-29) that play critical roles in host defense. To define the molecular mechanisms that regulate its promiscuous binding, we have determined the crystal structure of the IL-10R2 ectodomain at 2.14 A resolution. IL-10R2 residues required for binding were identified by alanine scanning and used to derive computational models of IL-10/IL-10R1/IL-10R2 and IL-22/IL-22R1/IL-10R2 ternary complexes. The models reveal a conserved binding epitope that is surrounded by two clefts that accommodate the structural and chemical diversity of the cytokines. These results provide a structural framework for interpreting IL-10R2 single nucleotide polymorphisms associated with human disease.
Structure and mechanism of receptor sharing by the IL-10R2 common chain.,Yoon SI, Jones BC, Logsdon NJ, Harris BD, Deshpande A, Radaeva S, Halloran BA, Gao B, Walter MR Structure. 2010 May 12;18(5):638-48. PMID:20462497[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Sheppard P, Kindsvogel W, Xu W, Henderson K, Schlutsmeyer S, Whitmore TE, Kuestner R, Garrigues U, Birks C, Roraback J, Ostrander C, Dong D, Shin J, Presnell S, Fox B, Haldeman B, Cooper E, Taft D, Gilbert T, Grant FJ, Tackett M, Krivan W, McKnight G, Clegg C, Foster D, Klucher KM. IL-28, IL-29 and their class II cytokine receptor IL-28R. Nat Immunol. 2003 Jan;4(1):63-8. Epub 2002 Dec 2. PMID:12469119 doi:10.1038/ni873
- ↑ Donnelly RP, Sheikh F, Kotenko SV, Dickensheets H. The expanded family of class II cytokines that share the IL-10 receptor-2 (IL-10R2) chain. J Leukoc Biol. 2004 Aug;76(2):314-21. Epub 2004 May 3. PMID:15123776 doi:http://dx.doi.org/10.1189/jlb.0204117
- ↑ Yoon SI, Jones BC, Logsdon NJ, Harris BD, Deshpande A, Radaeva S, Halloran BA, Gao B, Walter MR. Structure and mechanism of receptor sharing by the IL-10R2 common chain. Structure. 2010 May 12;18(5):638-48. PMID:20462497 doi:10.1016/j.str.2010.02.009
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