4GS7: Structure of the Interleukin-15 Quaternary Complex

Citation:
Abstract
Interleukin 15 (IL-15) and IL-2 have distinct immunological functions even though both signal through the receptor subunit IL-2Rbeta and the common gamma-chain (gamma(c)). Here we found that in the structure of the IL-15-IL-15Ralpha-IL-2Rbeta-gamma(c) quaternary complex, IL-15 binds to IL-2Rbeta and gamma(c) in a heterodimer nearly indistinguishable from that of the IL-2-IL-2Ralpha-IL-2Rbeta-gamma(c) complex, despite their different receptor-binding chemistries. IL-15Ralpha substantially increased the affinity of IL-15 for IL-2Rbeta, and this allostery was required for IL-15 trans signaling. Consistent with their identical IL-2Rbeta-gamma(c) dimer geometries, IL-2 and IL-15 showed similar signaling properties in lymphocytes, with any differences resulting from disparate receptor affinities. Thus, IL-15 and IL-2 induced similar signals, and the cytokine specificity of IL-2Ralpha versus IL-15Ralpha determined cellular responsiveness. Our results provide new insights for the development of specific immunotherapeutics based on IL-15 or IL-2.
PDB ID: 4GS7Download
MMDB ID: 104804
PDB Deposition Date: 2012/8/27
Updated in MMDB: 2012/12
Experimental Method:
x-ray diffraction
Resolution: 2.35  Å
Source Organism:
Similar Structures:
Biological Unit for 4GS7: tetrameric; determined by author and by software (PISA)
Molecular Components in 4GS7
Label Count Molecule
Proteins (4 molecules)
1
Interleukin-15(Gene symbol: IL15)
Molecule annotation
1
Interleukin-2 Receptor Subunit Beta(Gene symbol: IL2RB)
Molecule annotation
1
Cytokine Receptor Common Subunit Gamma(Gene symbol: IL2RG)
Molecule annotation
1
Interleukin-15 Receptor Subunit Alpha(Gene symbol: IL15RA)
Molecule annotation
Chemicals (8 molecules)
1
1
2
6
3
1
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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