The structure of the IL-15alpha -receptor and its implications for ligand binding

doi:10.1074/jbc.M513118200

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A more recent version of this article appeared on March 10, 2006 Originally published In Press as doi:10.1074/jbc.M513118200 on January 5, 2006

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Papers In Press, published online ahead of print December 23, 2005
J. Biol. Chem, 10.1074/jbc.M513118200
Submitted on December 8, 2005
Accepted on December 23, 2005

The structure of the IL-15 $alpha$ -receptor and its implications for ligand binding

Inken Lorenzen, Andrew J. Dingley, Yannick Jaques, and Joachim Grötzinger

Biochemistry Dept., University of Kiel, Kiel 24098

Corresponding Author: jgroetzinger{at}biochem.uni-kiel.de

Interleukin-15 (IL-15) is a member of the small four a-helix bundle family of cytokines. IL-15 was discovered by its ability to mimic Interleukin-2 (IL-2) mediated T cell-proliferation. Both cytokines share the b-and g-receptor chains of the IL-2 receptor for signaltransduction. However, in addition they target specific a-chain receptors, the IL-15Ra and IL-2Ra, respectively. The exceptionally high-affinity binding of IL-15 to the IL-15Ra is mediated by its sushi domain. Here we present the solution structure of the IL-15Ra sushi domain solved by NMR spectroscopy and a model of its complex with IL-15. The model shows that rather than the familiar hydrophobic forces dominating the interaction interface between cytokines and their cognate receptors, the interaction between IL-15 and IL-15Ra complex involves a large network of ionic interactions. This type of interaction explains the exceptionally high affinity of the IL-15/IL-15Ra complex, which is essential for the biological effects of this important cytokine and that is not observed in other cytokine/cytokine receptor complexes.

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The structure of the IL-15-receptor and its implications for ligand binding

The structure of the IL-15 $alpha$ -receptor and its implications for ligand binding