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3bpo

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3bpo, resolution 3.00Å ()
Ligands:
Gene: IL13 (Homo sapiens), IL4R, 582J2.1, IL4RA (Homo sapiens), IL13RA1, IL13R, IL13RA (Homo sapiens)
Related: 3bpl, 3bpn
Resources: FirstGlance, OCA, RCSB, PDBsum
Coordinates: save as pdb, mmCIF, xml


Contents

Crystal structure of the IL13-IL4R-IL13Ra ternary complex

Publication Abstract from PubMed

Interleukin-4 and Interleukin-13 are cytokines critical to the development of T cell-mediated humoral immune responses, which are associated with allergy and asthma, and exert their actions through three different combinations of shared receptors. Here we present the crystal structures of the complete set of type I (IL-4R alpha/gamma(c)/IL-4) and type II (IL-4R alpha/IL-13R alpha1/IL-4, IL-4R alpha/IL-13R alpha1/IL-13) ternary signaling complexes. The type I complex reveals a structural basis for gamma(c)'s ability to recognize six different gamma(c)-cytokines. The two type II complexes utilize an unusual top-mounted Ig-like domain on IL-13R alpha1 for a novel mode of cytokine engagement that contributes to a reversal in the IL-4 versus IL-13 ternary complex assembly sequences, which are mediated through substantially different recognition chemistries. We also show that the type II receptor heterodimer signals with different potencies in response to IL-4 versus IL-13 and suggest that the extracellular cytokine-receptor interactions are modulating intracellular membrane-proximal signaling events.

Molecular and structural basis of cytokine receptor pleiotropy in the interleukin-4/13 system., LaPorte SL, Juo ZS, Vaclavikova J, Colf LA, Qi X, Heller NM, Keegan AD, Garcia KC, Cell. 2008 Jan 25;132(2):259-72. PMID:18243101

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

Function

[I13R1_HUMAN] Binds with low affinity to interleukin-13 (IL13). Together with IL4RA can form a functional receptor for IL13. Also serves as an alternate accessory protein to the common cytokine receptor gamma chain for interleukin-4 (IL4) signaling, but cannot replace the function of IL2RG in allowing enhanced interleukin-2 (IL2) binding activity. [IL4RA_HUMAN] Receptor for both interleukin 4 and interleukin 13. Couples to the JAK1/2/3-STAT6 pathway. The IL4 response is involved in promoting Th2 differentiation. The IL4/IL13 responses are involved in regulating IgE production and, chemokine and mucus production at sites of allergic inflammation. In certain cell types, can signal through activation of insulin receptor substrates, IRS1/IRS2.[1] Soluble IL4R (sIL4R) inhibits IL4-mediated cell proliferation and IL5 up-regulation by T-cells.[2]

About this Structure

3bpo is a 3 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA.

See Also

Reference

  • LaPorte SL, Juo ZS, Vaclavikova J, Colf LA, Qi X, Heller NM, Keegan AD, Garcia KC. Molecular and structural basis of cytokine receptor pleiotropy in the interleukin-4/13 system. Cell. 2008 Jan 25;132(2):259-72. PMID:18243101 doi:10.1016/j.cell.2007.12.030
  1. Keegan AD, Nelms K, White M, Wang LM, Pierce JH, Paul WE. An IL-4 receptor region containing an insulin receptor motif is important for IL-4-mediated IRS-1 phosphorylation and cell growth. Cell. 1994 Mar 11;76(5):811-20. PMID:8124718
  2. Keegan AD, Nelms K, White M, Wang LM, Pierce JH, Paul WE. An IL-4 receptor region containing an insulin receptor motif is important for IL-4-mediated IRS-1 phosphorylation and cell growth. Cell. 1994 Mar 11;76(5):811-20. PMID:8124718

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