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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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Contents |
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* Residue conservation analysis
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DOI no:
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J Biol Chem
281:6642-6647
(2006)
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PubMed id:
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The structure of the interleukin-15 alpha receptor and its implications for ligand binding.
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I.Lorenzen,
A.J.Dingley,
Y.Jacques,
J.Grötzinger.
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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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Selected figure(s)
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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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Figures were
selected
by an automated process.
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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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J.Scheller,
A.Chalaris,
D.Schmidt-Arras,
and
S.Rose-John
(2011).
The pro- and anti-inflammatory properties of the cytokine interleukin-6.
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Biochim Biophys Acta,
1813,
878-888.
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J.Suthaus,
N.Adam,
J.Grötzinger,
J.Scheller,
and
S.Rose-John
(2011).
Viral Interleukin-6: Structure, pathophysiology and strategies of neutralization.
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Eur J Cell Biol,
90,
495-504.
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A.Israni,
R.Leduc,
J.Holmes,
P.A.Jacobson,
V.Lamba,
W.Guan,
D.Schladt,
J.Chen,
A.J.Matas,
W.S.Oetting,
J.M.Cecka,
J.Connett,
F.G.Cosio,
R.Gaston,
S.Gourishankar,
J.P.Grande,
L.Hunsicker,
B.Kasiske,
R.Mannon,
and
D.Rush
(2010).
Single-nucleotide polymorphisms, acute rejection, and severity of tubulitis in kidney transplantation, accounting for center-to-center variation.
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Transplantation,
90,
1401-1408.
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H.Eini,
N.Tejman-Yarden,
E.C.Lewis,
C.Chaimovitz,
M.Zlotnik,
and
A.Douvdevani
(2010).
Association between renal injury and reduced interleukin-15 and interleukin-15 receptor levels in acute kidney injury.
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J Interferon Cytokine Res,
30,
1-8.
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J.Suthaus,
A.Tillmann,
I.Lorenzen,
E.Bulanova,
S.Rose-John,
and
J.Scheller
(2010).
Forced homo- and heterodimerization of all gp130-type receptor complexes leads to constitutive ligand-independent signaling and cytokine-independent growth.
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Mol Biol Cell,
21,
2797-2807.
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S.W.Stonier,
and
K.S.Schluns
(2010).
Trans-presentation: a novel mechanism regulating IL-15 delivery and responses.
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Immunol Lett,
127,
85-92.
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X.Wang,
P.Lupardus,
S.L.Laporte,
and
K.C.Garcia
(2009).
Structural biology of shared cytokine receptors.
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Annu Rev Immunol,
27,
29-60.
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E.H.Duitman,
Z.Orinska,
E.Bulanova,
R.Paus,
and
S.Bulfone-Paus
(2008).
How a cytokine is chaperoned through the secretory pathway by complexing with its own receptor: lessons from interleukin-15 (IL-15)/IL-15 receptor alpha.
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Mol Cell Biol,
28,
4851-4861.
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H.P.Carroll,
V.Paunovic,
and
M.Gadina
(2008).
Signalling, inflammation and arthritis: Crossed signals: the role of interleukin-15 and -18 in autoimmunity.
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Rheumatology (Oxford),
47,
1269-1277.
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M.Chirifu,
C.Hayashi,
T.Nakamura,
S.Toma,
T.Shuto,
H.Kai,
Y.Yamagata,
S.J.Davis,
and
S.Ikemizu
(2007).
Crystal structure of the IL-15-IL-15Ralpha complex, a cytokine-receptor unit presented in trans.
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Nat Immunol,
8,
1001-1007.
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PDB codes:
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S.Vucetic,
H.Xie,
L.M.Iakoucheva,
C.J.Oldfield,
A.K.Dunker,
Z.Obradovic,
and
V.N.Uversky
(2007).
Functional anthology of intrinsic disorder. 2. Cellular components, domains, technical terms, developmental processes, and coding sequence diversities correlated with long disordered regions.
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J Proteome Res,
6,
1899-1916.
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M.P.Rubinstein,
M.Kovar,
J.F.Purton,
J.H.Cho,
O.Boyman,
C.D.Surh,
and
J.Sprent
(2006).
Converting IL-15 to a superagonist by binding to soluble IL-15R{alpha}.
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Proc Natl Acad Sci U S A,
103,
9166-9171.
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O.Hecht,
A.J.Dingley,
A.Schwanter,
S.Ozbek,
S.Rose-John,
and
J.Grötzinger
(2006).
The solution structure of the membrane-proximal cytokine receptor domain of the human interleukin-6 receptor.
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Biol Chem,
387,
1255-1259.
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PDB code:
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The most recent references are shown first.
Citation data come partly from CiteXplore and partly
from an automated harvesting procedure. Note that this is likely to be
only a partial list as not all journals are covered by
either method. However, we are continually building up the citation data
so more and more references will be included with time.
Where a reference describes a PDB structure, the PDB
codes are
shown on the right.
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Links
