3lb6
From Proteopedia
The structure of IL-13 in complex with IL-13Ralpha2
Structural highlights
Disease[IL13_HUMAN] Defects in IL13 may be a cause of susceptibility to allergic rhinitis (ALRH) [MIM:607154]. Allergic rhinitis is a common disease of complex inheritance and is characterized by mucosal inflammation caused by allergen exposure. Function[I13R2_HUMAN] Binds as a monomer with high affinity to interleukin-13 (IL13), but not to interleukin-4 (IL4).[1] [IL13_HUMAN] Cytokine. Inhibits inflammatory cytokine production. Synergizes with IL2 in regulating interferon-gamma synthesis. May be critical in regulating inflammatory and immune responses. 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 PubMedInterleukin-13 is a cytokine important for development of T helper cell type 2 (Th2) responses and plays a critical role in asthma and allergy. The IL-13 Receptor alpha2 (IL-13Ralpha2) is a receptor for IL-13 lacking canonical Jak/STAT signaling functions. Here we present the crystal structure along with a mutational and biophysical analysis of the IL-13/IL-13Ralpha2 complex. While retaining a similar mode of IL-13 binding to its related signaling receptor, IL-13Ralpha1, IL-13Ralpha2 uses peripheral receptor residues unused in the IL-13/IL-13Ralpha1 complex to generate a larger and more complementary interface for IL-13. This results in a four orders of magnitude increase in affinity, to the femtomolar level, compared to IL-13Ralpha1. Alanine scanning mutagenesis of the IL-13 interface reveals several common "hotspot" residues important for binding to both receptors, but also identifies a prominent IL-13Ralpha2-specific contact. These results provide a framework for development of receptor subtype-selective IL-13 antagonists and indicate a decoy function for IL-13Ralpha2. Molecular basis for shared cytokine recognition revealed in the structure of an unusually high affinity complex between IL-13 and IL-13Ralpha2.,Lupardus PJ, Birnbaum ME, Garcia KC Structure. 2010 Mar 10;18(3):332-42. PMID:20223216[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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