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PDBsum entry 2z3q
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Cytokine/cytokine receptor
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PDB id
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2z3q
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Contents |
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114 a.a.
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81 a.a.
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117 a.a.
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77 a.a.
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References listed in PDB file
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Key reference
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Title
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Crystal structure of the il-15-Il-15ralpha complex, A cytokine-Receptor unit presented in trans.
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Authors
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M.Chirifu,
C.Hayashi,
T.Nakamura,
S.Toma,
T.Shuto,
H.Kai,
Y.Yamagata,
S.J.Davis,
S.Ikemizu.
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Ref.
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Nat Immunol, 2007,
8,
1001-1007.
[DOI no: ]
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PubMed id
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Abstract
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Interleukin 15 (IL-15) and IL-2, which promote the survival of memory CD8(+) T
cells and regulatory T cells, respectively, bind receptor complexes that share
beta- and gamma-signaling subunits. Receptor specificity is provided by unique,
nonsignaling alpha-subunits. Whereas IL-2 receptor-alpha (IL-2Ralpha) is
expressed together in cis with the beta- and gamma-subunits on T cells and B
cells, IL-15Ralpha is expressed in trans on antigen-presenting cells. Here we
present a 1.85-A crystal structure of the human IL-15-IL-15Ralpha complex. The
structure provides insight into the molecular basis of the specificity of
cytokine recognition and emphasizes the importance of water in generating this
very high-affinity complex. Despite very low IL-15-IL-2 sequence homology and
distinct receptor architecture, the topologies of the IL-15-IL-15Ralpha and
IL-2-IL-2Ralpha complexes are very similar. Our data raise the possibility that
IL-2, like IL-15, might be capable of being presented in trans in the context of
its unique receptor alpha-chain.
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Figure 1.
(a) Two IL-15–IL-15R complexes
in the asymmetric unit of the P2[1]2[1]2 crystal form. One IL-15
molecule (magenta) forms a complex with one IL-15R molecule
(cyan), which then associates with another complex of IL-15
(blue) and IL-15R (red).
These two complexes have a noncrystallographic twofold
relationship. (b) Superposition of dimers of IL-15–IL15R complexes
from the P2[1]2[1]2 (red) and P2[1]2[1]2[1] (blue) crystals.
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Figure 4.
(a) The IL-15–IL-15R complex:
magenta, IL-15; cyan, IL-15R .
The interface is divided into three regions (outlined): top,
middle and bottom.
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The above figures are
reprinted
by permission from Macmillan Publishers Ltd:
Nat Immunol
(2007,
8,
1001-1007)
copyright 2007.
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