3BPO: Crystal Structure Of The Il13-Il4r-Il13ra Ternary Complex

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.
PDB ID: 3BPODownload
MMDB ID: 62307
PDB Deposition Date: 2007/12/18
Updated in MMDB: 2012/11
Experimental Method:
x-ray diffraction
Resolution: 3  Å
Source Organism:
Similar Structures:
Biological Unit for 3BPO: trimeric; determined by author and by software (PISA)
Molecular Components in 3BPO
Label Count Molecule
Proteins (3 molecules)
Interleukin 13
Molecule annotation
Interleukin-4 Receptor Alpha Chain(Gene symbol: IL4R)
Molecule annotation
Interleukin-13 Receptor Alpha-1 Chain(Gene symbol: IL13RA1)
Molecule annotation
Chemicals (3 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB