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PDBsum entry 1evs
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DOI no:
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Structure
8:863-874
(2000)
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PubMed id:
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Crystal structure and functional dissection of the cytostatic cytokine oncostatin M.
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M.C.Deller,
K.R.Hudson,
S.Ikemizu,
J.Bravo,
E.Y.Jones,
J.K.Heath.
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ABSTRACT
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BACKGROUND: The cytokine oncostatin M (OSM) inhibits growth of certain
tumour-derived cells, induces proliferation in other cell types (e.g.
haemangioblasts) and is a mediator of inflammatory responses. Its mechanism of
action is via specific binding to gp130 and either the leukaemia inhibitory
factor receptor (LIFR) or oncostatin M receptor (OSMR) systems at the cell
surface to form an active signalling complex. RESULTS: We report here the
crystal structure of human oncostatin M (hOSM) along with mutagenesis data which
map the receptor-binding epitopes of the molecule. The structure was determined
to a resolution of 2.2 A and conforms to the haematopoietin cytokine
up-up-down-down four-helix bundle topology. The site 2 epitope, responsible for
gp130 binding, is centred around Gly120 which forms a 'dimple' on the surface of
the molecule located on helices A and C. The site 3 motif, responsible for LIFR
and OSMR binding, consists of a protruding Phe160/Lys163 pair located at the
start of helix D. CONCLUSIONS: The data presented allow functional dissection of
the receptor-binding interfaces to atomic resolution. Modelling suggests that
the gp130 residue Phe169 packs into the site 2 dimple in an analogous fashion to
structurally equivalent residues at the growth hormone-growth hormone receptor
interface, implying that certain key features may underlie recognition across
the whole cytokine/receptor superfamily. Conversely, detailed comparison of the
available structures suggests that variations on a common theme dictate the
specificity of receptor-ligand interactions within the gp130 family of cytokines.
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Selected figure(s)
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Figure 5.
Figure 5. Complimentarity between the interaction surfaces
of hOSM and gp130. The solvent-accessible surfaces of site 2 on
hOSM (left) and the cognate binding site on gp130 (right) are
displayed with areas contributed by residues implicated in
binding highlighted as coloured patches. The orientation for
hOSM site 2 is rotated 90° from that in Figure 4 whereas gp130
is rotated by 180° from its orientation relative to hOSM in the
putative interaction complex, as in the opening of a book.
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The above figure is
reprinted
by permission from Cell Press:
Structure
(2000,
8,
863-874)
copyright 2000.
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Figure was
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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S.Le Saux,
F.Rousseau,
F.Barbier,
E.Ravon,
L.Grimaud,
Y.Danger,
J.Froger,
S.Chevalier,
and
H.Gascan
(2010).
Molecular dissection of human interleukin-31-mediated signal transduction through site-directed mutagenesis.
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J Biol Chem,
285,
3470-3477.
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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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U.Prisco,
C.Leung,
C.Xirouchaki,
C.H.Jones,
J.K.Heath,
and
R.E.Palmer
(2005).
Residue-specific immobilization of protein molecules by size-selected clusters.
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J R Soc Interface,
2,
169-175.
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H.Plun-Favreau,
D.Perret,
C.Diveu,
J.Froger,
S.Chevalier,
E.Lelièvre,
H.Gascan,
and
M.Chabbert
(2003).
Leukemia inhibitory factor (LIF), cardiotrophin-1, and oncostatin M share structural binding determinants in the immunoglobulin-like domain of LIF receptor.
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J Biol Chem,
278,
27169-27179.
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J.Bitard,
S.Daburon,
L.Duplomb,
F.Blanchard,
P.Vuisio,
Y.Jacques,
A.Godard,
J.K.Heath,
J.F.Moreau,
and
J.L.Taupin
(2003).
Mutations in the immunoglobulin-like domain of gp190, the leukemia inhibitory factor (LIF) receptor, increase or decrease its affinity for LIF.
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J Biol Chem,
278,
16253-16261.
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M.J.Boulanger,
A.J.Bankovich,
T.Kortemme,
D.Baker,
and
K.C.Garcia
(2003).
Convergent mechanisms for recognition of divergent cytokines by the shared signaling receptor gp130.
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Mol Cell,
12,
577-589.
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PDB code:
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D.Chow,
X.He,
A.L.Snow,
S.Rose-John,
and
K.C.Garcia
(2001).
Structure of an extracellular gp130 cytokine receptor signaling complex.
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Science,
291,
2150-2155.
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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
code is
shown on the right.
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