Interleukin-13 (IL-13)
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| Minimized Average IL-13 structure PDBID: 1IJZ Journal of Molecular Biology (2001), 310(1) 219-230. |
| IL-13 - IL-4-a
Complex Model The IL-13 is colored yellow and IL-4-a is colored red Model published in: Journal of Molecular Biology (2001), 310(1) 219-230. Created from: PDBID: 1IJZ and 1IRA. (Cell (1999) 97:271). |
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Interleukin-13 has been implicated as a key factor in asthma, allergy, atopy and inflammatory response establishing the protein as a valuable therapeutic target. IL-13 is produced by activated T cells and promotes B cell proliferation, induces B cells to produce IgE, down regulates the production of proinflamatory cytokines, increases expression of VCAM-1 on endothelial cells, enhances the expression of class II MHC antigens and various adhesion molecules on monocytes. IL-13 mediates these functions through an interaction with its receptor on hematopoietic and other cell types, but currently no functional receptors have been identified on T cells. The signaling human IL-13 receptor (IL-13R) is a heterodimer composed of the interleukin-4 receptor a chain (IL-4Ra) and the IL-13 binding chain. The association of IL-13 with its receptor induces the activation of STAT6 (signal transducer and activation of transcription 6) and Janus-family kinase (JAK1, JAK2, TYK2) through a binding interaction with the IL-4Ra chain.
IL-13 shares many functional properties with IL-4 as a result of the common IL-4Ra component in their receptors. IL-4 exhibits a high affinity to IL-4Ra chain (KD =20-300 pM) where this complex recruits the common g chain (gc) of IL-4R to form the signaling complex. Similarly, IL-13 binds to the IL-13 binding chain (IL-13Ra1) with relatively high affinity (KD ~ 4 nM) in the absence of the IL-4Ra chain, where an increase in affinity to IL-4R occurs in the presence of IL-4Ra (KD = 50 pM). IL-13 does not bind IL-4Ra in the absence of the IL-13 binding chain. As a result, IL-4 exhibits binding to both IL-4R and IL-13R due to the existence of the IL-4Ra chain in both receptors, but IL-13 does not bind IL-4R because of the absence of the IL-13 binding chain.
IL-13 and IL-4 are both members of the short chain four-helix bundle cytokine family. Despite the relatively low 25% sequence homology between IL-13 and IL-4, a similarity in the overall topology between the two proteins is expected. A combination of mutational and kinetic analysis has identified a distinct site on the IL-4 structure associated with IL-4Ra binding and a second site associated with signaling through the gc chain. Recently, the X-ray structure of IL-4 complexed with the ectodomain of IL-4Ra has been determined, which further defines the IL-4 - IL-4Ra interface. The resulting IL-13 NMR structure and assignments are consistent with previous short chain left-handed four-helix bundles where a significant similarity in the folding topology between IL-13 and IL-4 was observed. IL-13 shares a significant overlap in biological function with IL-4, a result of the common a chain component (IL-4Ra) in their respective receptors. Based on the available structural and mutational data, an IL-13/IL4Ra model and a sequential mechanism for forming the signaling heterodimer is proposed for IL-13 (IL-13 review).
See also the IL-4 and OM web pages.