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* Residue conservation analysis
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Gene Ontology (GO) functional annotation
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Cellular component
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extracellular region
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3 terms
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Biological process
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negative regulation of growth of symbiont in host
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51 terms
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Biochemical function
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cytokine activity
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3 terms
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DOI no:
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Structure
3:591-601
(1995)
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PubMed id:
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Crystal structure of interleukin-10 reveals the functional dimer with an unexpected topological similarity to interferon gamma.
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A.Zdanov,
C.Schalk-Hihi,
A.Gustchina,
M.Tsang,
J.Weatherbee,
A.Wlodawer.
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ABSTRACT
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BACKGROUND: Interleukin (IL)-10 is a cytokine that inhibits production of other
regulatory factors, including interferon gamma (IFN-gamma) and IL-2. A dimer of
IL-10 is present in solution and is presumed to participate in receptor binding,
but the nature of the dimer has not been previously reported. An atomic model is
necessary to interpret biological activity of IL-10 and to design mutants with
agonistic or antagonistic properties. RESULTS: The X-ray crystal structure of a
recombinant form of human IL-10 has been solved at 1.8 A resolution and refined
to a crystallographic R-factor of 0.156. The molecule is a tight dimer made of
two interpenetrating subunits, forming a V-shaped structure. Each half of the
structure consists of a six alpha-helices, four originating from one subunit and
two from the other. Four of the helices form a classical 'up-up-down-down'
bundle observed in all other helical cytokines. The overall topology of the
helices bears close resemblance to IFN gamma, although the similarity is less
striking when examined in greater detail. CONCLUSIONS: The topological
similarity of IL-10 to IFN gamma was totally unexpected, and may be a reflection
of the close relationship between the biological effects of these two cytokines.
The structure of IL-10 provides insights into the possible modes of conversion
of the dimer into monomers, and of putative sites of receptor interactions. The
good level of refinement and high resolution of this structure show that the
internal disorder often associated with other helical cytokines is not an
essential feature of this class of proteins.
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Selected figure(s)
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Figure 4.
Figure 4. Electron-density map (2F[o]−F[c]) for the
connecting strand between helices D and E, contoured at the
1.5σ level. The density for the side chains of Lys117 and
Lys119 is not seen. Figure 4. Electron-density map
(2F[o]−F[c]) for the connecting strand between helices D and
E, contoured at the 1.5σ level. The density for the side chains
of Lys117 and Lys119 is not seen. (Figure prepared with the
program CHAIN [[3]50].)
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Figure 7.
Figure 7. Comparison of a domain of IL-10 with long-chain
cytokines. (a) Superposition of the Cα coordinates of IL-10
(green) and bG-CSF (red). (b) Superposition of Cα coordinates
of IL-10 (green) and hGH (red). Receptor-binding sites of hGH
are marked in orange (site 1) and in blue (site 2). Figure 7.
Comparison of a domain of IL-10 with long-chain cytokines. (a)
Superposition of the Cα coordinates of IL-10 (green) and bG-CSF
(red). (b) Superposition of Cα coordinates of IL-10 (green) and
hGH (red). Receptor-binding sites of hGH are marked in orange
(site 1) and in blue (site 2). (Figure prepared with the program
CHAIN [[4]50].)
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The above figures are
reprinted
by permission from Cell Press:
Structure
(1995,
3,
591-601)
copyright 1995.
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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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PDB code:
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PDB code:
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| |
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| |
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(1998).
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| |
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(1997).
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|
| |
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|
PDB code:
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|
|
A.Zdanov,
C.Schalk-Hihi,
and
A.Wlodawer
(1996).
Crystal structure of human interleukin-10 at 1.6 A resolution and a model of a complex with its soluble receptor.
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Protein Sci, 5,
1955-1962.
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PDB code:
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J.J.Tanner,
B.Lei,
S.C.Tu,
and
K.L.Krause
(1996).
Flavin reductase P: structure of a dimeric enzyme that reduces flavin.
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Biochemistry, 35,
13531-13539.
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PDB code:
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R.Radhakrishnan,
L.J.Walter,
A.Hruza,
P.Reichert,
P.P.Trotta,
T.L.Nagabhushan,
and
M.R.Walter
(1996).
Zinc mediated dimer of human interferon-alpha 2b revealed by X-ray crystallography.
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Structure, 4,
1453-1463.
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PDB code:
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U.Reineke,
R.Sabat,
A.Kramer,
R.D.Stigler,
M.Seifert,
T.Michel,
H.D.Volk,
and
J.Schneider-Mergener
(1996).
Mapping protein-protein contact sites using cellulose-bound peptide scans.
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Mol Divers, 1,
141-148.
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M.J.Bennett,
M.P.Schlunegger,
and
D.Eisenberg
(1995).
3D domain swapping: a mechanism for oligomer assembly.
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Protein Sci, 4,
2455-2468.
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R.J.Fletterick,
and
J.F.Bazan
(1995).
When one and one are not two.
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Nat Struct Biol, 2,
721-723.
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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
code is
shown on the right.
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Links
