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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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* Residue conservation analysis
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PDB id:
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Cytokine/cytokine receptor
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Title:
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Crystal structure of the il-15/il-15ra complex
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Structure:
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Interleukin-15. Chain: a, c. Synonym: il-15. Engineered: yes. Interleukin-15 receptor alpha chain. Chain: b, d. Fragment: il-15ra, residues in database 31-132. Synonym: il-15r-alpha, il- 15ra. Engineered: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Gene: il15. Expressed in: escherichia coli. Expression_system_taxid: 562. Gene: il15ra.
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Resolution:
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1.85Å
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R-factor:
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0.205
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R-free:
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0.252
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Authors:
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M.Chirifu,Y.Yamagata,S.J.Davis,S.Ikemizu
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Key ref:
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M.Chirifu
et al.
(2007).
Crystal structure of the IL-15-IL-15Ralpha complex, a cytokine-receptor unit presented in trans.
Nat Immunol,
8,
1001-1007.
PubMed id:
DOI:
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Date:
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05-Jun-07
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Release date:
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04-Sep-07
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PROCHECK
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Headers
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References
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P40933
(IL15_HUMAN) -
Interleukin-15 from Homo sapiens
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Seq:
Struc:
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162 a.a.
114 a.a.*
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Q13261
(I15RA_HUMAN) -
Interleukin-15 receptor subunit alpha from Homo sapiens
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Seq:
Struc:
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267 a.a.
81 a.a.*
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DOI no:
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Nat Immunol
8:1001-1007
(2007)
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PubMed id:
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Crystal structure of the IL-15-IL-15Ralpha complex, a cytokine-receptor unit presented in trans.
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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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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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Selected figure(s)
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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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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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G.Béhar,
V.Solé,
A.Defontaine,
M.Maillasson,
A.Quéméner,
Y.Jacques,
and
C.Tellier
(2011).
Evolution of interleukin-15 for higher E. coli expression and solubility.
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Protein Eng Des Sel,
24,
283-290.
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R.L.Wong,
B.Liu,
X.Zhu,
L.You,
L.Kong,
K.P.Han,
H.I.Lee,
P.A.Chavaillaz,
M.Jin,
Y.Wang,
P.R.Rhode,
and
H.C.Wong
(2011).
Interleukin-15:Interleukin-15 receptor {alpha} scaffold for creation of multivalent targeted immune molecules.
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Protein Eng Des Sel,
24,
373-383.
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J.E.Lee,
M.L.Fusco,
and
E.Ollmann Saphire
(2009).
An efficient platform for screening expression and crystallization of glycoproteins produced in human cells.
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Nat Protoc,
4,
592-604.
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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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X.Zhu,
W.D.Marcus,
W.Xu,
H.I.Lee,
K.Han,
J.O.Egan,
J.L.Yovandich,
P.R.Rhode,
and
H.C.Wong
(2009).
Novel human interleukin-15 agonists.
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J Immunol,
183,
3598-3607.
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C.A.Sabatos,
J.Doh,
S.Chakravarti,
R.S.Friedman,
P.G.Pandurangi,
A.J.Tooley,
and
M.F.Krummel
(2008).
A synaptic basis for paracrine interleukin-2 signaling during homotypic T cell interaction.
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Immunity,
29,
238-248.
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E.Mortier,
T.Woo,
R.Advincula,
S.Gozalo,
and
A.Ma
(2008).
IL-15Ralpha chaperones IL-15 to stable dendritic cell membrane complexes that activate NK cells via trans presentation.
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J Exp Med,
205,
1213-1225.
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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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S.L.LaPorte,
Z.S.Juo,
J.Vaclavikova,
L.A.Colf,
X.Qi,
N.M.Heller,
A.D.Keegan,
and
K.C.Garcia
(2008).
Molecular and structural basis of cytokine receptor pleiotropy in the interleukin-4/13 system.
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Cell,
132,
259-272.
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PDB codes:
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S.K.Olsen,
N.Ota,
S.Kishishita,
M.Kukimoto-Niino,
K.Murayama,
H.Uchiyama,
M.Toyama,
T.Terada,
M.Shirouzu,
O.Kanagawa,
and
S.Yokoyama
(2007).
Crystal Structure of the Interleukin-15{middle dot}Interleukin-15 Receptor {alpha} Complex: INSIGHTS INTO TRANS AND CIS PRESENTATION.
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J Biol Chem,
282,
37191-37204.
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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
