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PDBsum entry 1j0s
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Contents |
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* Residue conservation analysis
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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 and binding mode of interleukin-18.
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Authors
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Z.Kato,
J.Jee,
H.Shikano,
M.Mishima,
I.Ohki,
H.Ohnishi,
A.Li,
K.Hashimoto,
E.Matsukuma,
K.Omoya,
Y.Yamamoto,
T.Yoneda,
T.Hara,
N.Kondo,
M.Shirakawa.
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Ref.
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Nat Struct Biol, 2003,
10,
966-971.
[DOI no: ]
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PubMed id
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Abstract
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Interleukin-18 (IL-18), a cytokine formerly known as interferon-gamma-
(IFN-gamma-) inducing factor, has pleiotropic immunoregulatory functions,
including augmentation of IFN-gamma production, Fas-mediated cytotoxicity and
developmental regulation of T-lymphocyte helper type I. We determined the
solution structure of IL-18 as a first step toward understanding its receptor
activation mechanism. It folds into a beta-trefoil structure that resembles that
of IL-1. Extensive mutagenesis revealed the presence of three sites that are
important for receptor activation: two serve as binding sites for IL-18 receptor
alpha (IL-18Ralpha), located at positions similar to those of IL-1 for IL-1
receptor type I (IL-1RI), whereas the third site may be involved in IL-18
receptor beta (IL-18Rbeta) binding. The structure and mutagenesis data provide a
basis for understanding the IL-18-induced heterodimerization of receptor
subunits, which is necessary for receptor activation.
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Figure 1.
Figure 1. Solution structure of human IL-18. (a) Stereo view
of the best-fit backbone superposition of the 20 final
structures. The backbone atoms of residues 1 -157 are
superimposed. (b) Schematic ribbon drawing of the NMR structure
of IL-18, drawn with MolMol30.
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Figure 3.
Figure 3. Models for the complex of IL-18 and IL-18R  ,
and interactions among IL-18, IL-18R and
IL-18R  .
(a) Crystal structure of the complex of IL-1  and
IL-1RI (PDB entry 1ITB). IL-1 residues
in sites A and B are red and orange, respectively. (b) Modeled
structure of the complex of IL-18 and IL-18R  .
IL-18 residues in sites I, II and III are red, orange and blue,
respectively. In a and b, the molecule on the right is viewed as
rotated by 90° about the vertical axis relative to the image on
the left. (c) Dose-response curves of surface plasmon resonance
for wild-type IL-18 to immobilized IL-18R or
to immobilized IL-18R .
Concentration of wild-type IL-18 is also indicated. (d) Response
curves of surface plasmon resonance for IL-18R for
to the complex of immobilized IL-18R with
wild-type IL-18 or the site III mutant proteins.
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The above figures are
reprinted
by permission from Macmillan Publishers Ltd:
Nat Struct Biol
(2003,
10,
966-971)
copyright 2003.
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