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PDBsum entry 2ers
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Signaling protein
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PDB id
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2ers
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References listed in PDB file
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Key reference
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Title
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The structure of the interleukin-15 alpha receptor and its implications for ligand binding.
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Authors
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I.Lorenzen,
A.J.Dingley,
Y.Jacques,
J.Grötzinger.
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Ref.
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J Biol Chem, 2006,
281,
6642-6647.
[DOI no: ]
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PubMed id
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Abstract
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Interleukin (IL)-15 is a member of the small four alpha-helix bundle family of
cytokines. IL-15 was discovered by its ability to mimic IL-2-mediated T-cell
proliferation. Both cytokines share the beta and gamma receptor chains of the
IL-2 receptor for signal transduction. However, in addition, they target
specific alpha chain receptors IL-15Ralpha and IL-2Ralpha, respectively. The
exceptionally high affinity binding of IL-15 to IL-15Ralpha is mediated by its
sushi domain. Here we present the solution structure of the IL-15Ralpha 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 the IL-15 and IL-15Ralpha complex involves a large network
of ionic interactions. This type of interaction explains the exceptionally high
affinity of the IL-15.IL-15Ralpha complex, which is essential for the biological
effects of this important cytokine and which is not observed in other
cytokine/cytokine receptor complexes.
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Figure 2.
The structure of the sushi domain of the IL-15Rα. A, ribbon
representation of the average energy-minimized structure. The
two disulfide bonds are yellow, and the N and C termini are
labeled. B, stereo view of 20 superimposed structures in
spaghetti representation and generated by distance geometry
calculations, N and C denotes the N and C termini, respectively.
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Figure 4.
Model of the IL-15 with its α receptor sushi domain as
ribbon representation. A, model of the complex of the sushi
domain (blue) and an IL-15 model (yellow). B, the proposed
binding interface between IL-15 and IL-15Rα.
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The above figures are
reprinted
by permission from the ASBMB:
J Biol Chem
(2006,
281,
6642-6647)
copyright 2006.
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