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101 a.a.
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215 a.a.
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220 a.a.
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* Residue conservation analysis
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PDB id:
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Immune system
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Title:
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Domain 4 of the beta common chain in complex with an antibody
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Structure:
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Cytokine receptor common beta chain precursor. Chain: a. Fragment: domain 4. Engineered: yes. Antibody (light chain). Chain: l. Antibody (heavy chain). Chain: h
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562. Mus musculus. House mouse. Organism_taxid: 10090. Other_details: monoclonal antibody.
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Biol. unit:
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Trimer (from
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Resolution:
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2.80Å
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R-factor:
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0.228
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R-free:
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0.288
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Authors:
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J.Rossjohn,W.J.Mckinstry,J.M.Woodcock,B.J.Mcclure,T.R.Hercus, M.W.Parker,A.F.Lopez,C.J.Bagley
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Key ref:
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J.Rossjohn
et al.
(2000).
Structure of the activation domain of the GM-CSF/IL-3/IL-5 receptor common beta-chain bound to an antagonist.
Blood,
95,
2491-2498.
PubMed id:
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Date:
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15-Feb-00
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Release date:
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15-Feb-01
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PROCHECK
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Headers
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References
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P32927
(IL3RB_HUMAN) -
Cytokine receptor common subunit beta from Homo sapiens
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Seq:
Struc:
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897 a.a.
101 a.a.
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Blood
95:2491-2498
(2000)
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PubMed id:
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Structure of the activation domain of the GM-CSF/IL-3/IL-5 receptor common beta-chain bound to an antagonist.
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J.Rossjohn,
W.J.McKinstry,
J.M.Woodcock,
B.J.McClure,
T.R.Hercus,
M.W.Parker,
A.F.Lopez,
C.J.Bagley.
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ABSTRACT
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Heterodimeric cytokine receptors generally consist of a major cytokine-binding
subunit and a signaling subunit. The latter can transduce signals by more than 1
cytokine, as exemplified by the granulocyte-macrophage colony-stimulating factor
(GM-CSF), interleukin-2 (IL-2), and IL-6 receptor systems. However, often the
signaling subunits in isolation are unable to bind cytokines, a fact that has
made it more difficult to obtain structural definition of their ligand-binding
sites. This report details the crystal structure of the ligand-binding domain of
the GM-CSF/IL-3/IL-5 receptor beta-chain (beta(c)) signaling subunit in complex
with the Fab fragment of the antagonistic monoclonal antibody, BION-1. This is
the first single antagonist of all 3 known eosinophil-producing cytokines, and
it is therefore capable of regulating eosinophil-related diseases such as
asthma. The structure reveals a fibronectin type III domain, and the
antagonist-binding site involves major contributions from the loop between the B
and C strands and overlaps the cytokine-binding site. Furthermore, tyrosine(421)
(Tyr(421)), a key residue involved in receptor activation, lies in the
neighboring loop between the F and G strands, although it is not immediately
adjacent to the cytokine-binding residues in the B-C loop. Interestingly,
functional experiments using receptors mutated across these loops demonstrate
that they are cooperatively involved in full receptor activation. The
experiments, however, reveal subtle differences between the B-C loop and
Tyr(421), which is suggestive of distinct functional roles. The elucidation of
the structure of the ligand-binding domain of beta(c) also suggests how
different cytokines recognize a single receptor subunit, which may have
implications for homologous receptor systems. (Blood. 2000;95:2491-2498)
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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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T.R.Hercus,
D.Thomas,
M.A.Guthridge,
P.G.Ekert,
J.King-Scott,
M.W.Parker,
and
A.F.Lopez
(2009).
The granulocyte-macrophage colony-stimulating factor receptor: linking its structure to cell signaling and its role in disease.
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Blood,
114,
1289-1298.
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G.Hansen,
T.R.Hercus,
B.J.McClure,
F.C.Stomski,
M.Dottore,
J.Powell,
H.Ramshaw,
J.M.Woodcock,
Y.Xu,
M.Guthridge,
W.J.McKinstry,
A.F.Lopez,
and
M.W.Parker
(2008).
The structure of the GM-CSF receptor complex reveals a distinct mode of cytokine receptor activation.
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Cell,
134,
496-507.
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PDB code:
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P.D.Carr,
F.Conlan,
S.Ford,
D.L.Ollis,
and
I.G.Young
(2006).
An improved resolution structure of the human beta common receptor involved in IL-3, IL-5 and GM-CSF signalling which gives better definition of the high-affinity binding epitope.
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Acta Crystallogr Sect F Struct Biol Cryst Commun,
62,
509-513.
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PDB code:
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M.Brines,
G.Grasso,
F.Fiordaliso,
A.Sfacteria,
P.Ghezzi,
M.Fratelli,
R.Latini,
Q.W.Xie,
J.Smart,
C.J.Su-Rick,
E.Pobre,
D.Diaz,
D.Gomez,
C.Hand,
T.Coleman,
and
A.Cerami
(2004).
Erythropoietin mediates tissue protection through an erythropoietin and common beta-subunit heteroreceptor.
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Proc Natl Acad Sci U S A,
101,
14907-14912.
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C.S.Clements,
H.H.Reid,
T.Beddoe,
F.E.Tynan,
M.A.Perugini,
T.G.Johns,
C.C.Bernard,
and
J.Rossjohn
(2003).
The crystal structure of myelin oligodendrocyte glycoprotein, a key autoantigen in multiple sclerosis.
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Proc Natl Acad Sci U S A,
100,
11059-11064.
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PDB code:
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H.S.Ramshaw,
J.M.Woodcock,
C.J.Bagley,
B.J.McClure,
T.R.Hercus,
and
A.F.Lopez
(2001).
New approaches in the treatment of asthma.
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Immunol Cell Biol,
79,
154-159.
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P.D.Carr,
S.E.Gustin,
A.P.Church,
J.M.Murphy,
S.C.Ford,
D.A.Mann,
D.M.Woltring,
I.Walker,
D.L.Ollis,
and
I.G.Young
(2001).
Structure of the complete extracellular domain of the common beta subunit of the human GM-CSF, IL-3, and IL-5 receptors reveals a novel dimer configuration.
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Cell,
104,
291-300.
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PDB code:
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S.E.Gustin,
A.P.Church,
S.C.Ford,
D.A.Mann,
P.D.Carr,
D.L.Ollis,
and
I.G.Young
(2001).
Expression, crystallization and derivatization of the complete extracellular domain of the beta(c) subunit of the human IL-5, IL-3 and GM-CSF receptors.
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Eur J Biochem,
268,
2905-2911.
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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
