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Contents |
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298 a.a.
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163 a.a.
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201 a.a.
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* Residue conservation analysis
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PDB id:
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Signaling protein/cytokine
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Title:
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Crystal structure of the hexameric human il-6/il-6 alpha receptor/gp130 complex
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Structure:
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Interleukin-6 receptor beta chain. Chain: a. Fragment: extracellular domains d1 - d3. Synonym: il-6r-beta, interleukin 6 signal transducer, membrane glycoprotein 130, gp130, oncostatin m receptor, cdw130, cd130 antigen. Engineered: yes. Interleukin-6. Chain: b.
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Gene: il6st. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Gene: il6 or ifnb2. Gene: il6r.
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Biol. unit:
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Hexamer (from PDB file)
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Resolution:
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3.65Å
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R-factor:
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0.282
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R-free:
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0.334
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Authors:
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M.J.Boulanger,D.C.Chow,E.E.Brevnova,K.C.Garcia
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Key ref:
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M.J.Boulanger
et al.
(2003).
Hexameric structure and assembly of the interleukin-6/IL-6 alpha-receptor/gp130 complex.
Science,
300,
2101-2104.
PubMed id:
DOI:
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Date:
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12-May-03
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Release date:
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01-Jul-03
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PROCHECK
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Headers
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References
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P40189
(IL6RB_HUMAN) -
Interleukin-6 receptor subunit beta from Homo sapiens
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Seq:
Struc:
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918 a.a.
298 a.a.
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DOI no:
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Science
300:2101-2104
(2003)
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PubMed id:
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Hexameric structure and assembly of the interleukin-6/IL-6 alpha-receptor/gp130 complex.
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M.J.Boulanger,
D.C.Chow,
E.E.Brevnova,
K.C.Garcia.
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ABSTRACT
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Interleukin-6 (IL-6) is an immunoregulatory cytokine that activates a
cell-surface signaling assembly composed of IL-6, the IL-6 alpha-receptor
(IL-6Ralpha), and the shared signaling receptor gp130. The 3.65
angstrom-resolution structure of the extracellular signaling complex reveals a
hexameric, interlocking assembly mediated by a total of 10 symmetry-related,
thermodynamically coupled interfaces. Assembly of the hexameric complex occurs
sequentially: IL-6 is first engaged by IL-6Ralpha and then presented to gp130in
the proper geometry to facilitate a cooperative transition into the
high-affinity, signaling-competent hexamer. The quaternary structures of other
IL-6/IL-12 family signaling complexes are likely constructed by means of a
similar topological blueprint.
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Selected figure(s)
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Figure 1.
Fig. 1. Structure of the human Il-6/IL-6R  /gp130 hexameric
complex. (A) Schematized view of the domain structure of IL-6,
IL-6R , and gp130. (B)
Top view of a SigmaA-weighted 2F[obs] - F[calc] electron density
map contoured at 2  of the hexamer.
The gp130 molecules are colored in cyan and blue, IL-6R molecules are
colored green and purple, and IL-6 molecules are colored pink
and red. The coloring scheme is maintained in all figures. (C)
Tilted side view of the hexamer rotated  90° toward the
viewer and tilted on the diagonal from (B). The five unique
interfaces are labeled as sites I, IIa, IIb, IIIa, and IIIb.
Figures were prepared with MOLSCRIPT (21) and Raster3D (22).
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Figure 3.
Fig. 3. Stepwise energetic and structural assembly of the
functional human IL-6 hexamer signaling complex. Isothermal
titration calorimetry (ITC) was used to measure the
thermodynamic parameters for each step in the hexamer assembly
pathway. The ITC titrations are designated as follows: site I:
IL-6 and IL-6R forming a binary
complex; site II: single-chain (sc) IL-6/IL-6R and gp130 D2D3
form a nonsignaling binary complex in the absence of the gp130
D1 domain; sites II and III: scIL-6/IL-6R and gp130 D1D2D3
form the signaling-competent hexamer; sites II and III 6 domain:
scIL-6/IL-6R and gp130
D1D2D3D4D5D6 resulting in the hexamer with the three
membrane-proximal domains of gp130. As discussed in the text,
the single-chain version of the IL-6/R complex was used
for these measurements to deconvolute the trimolecular
equilibrium (i.e., IL-6 + IL-6R + gp130) into a
bimolecular interaction event (i.e., single-chain IL-6/IL-6R
+ gp130).
Thermodynamic parameters for each titration are provided in
tabular format. Surfaces are calculated from the coordinates of
the hexamer components. The D1 domains of IL-6R are included as
schematic modules.
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The above figures are
reprinted
by permission from the AAAs:
Science
(2003,
300,
2101-2104)
copyright 2003.
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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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The structure of the unliganded extracellular domain of the interleukin-6 signal transducer gp130 in solution.
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PDB code:
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Proc Natl Acad Sci U S A,
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PDB code:
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A.Gertler
(2006).
Development of leptin antagonists and their potential use in experimental biology and medicine.
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Mol Biol Cell,
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J Virol,
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J Periodontol,
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The solution structure of the membrane-proximal cytokine receptor domain of the human interleukin-6 receptor.
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PDB code:
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Proc Natl Acad Sci U S A,
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PDB code:
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A.Schroers,
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Proteins,
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E.Honjo,
T.Tamada,
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PDB code:
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Y.H.Hamid,
C.S.Rose,
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Molecular recognition of BMP-2 and BMP receptor IA.
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Nat Struct Mol Biol,
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PDB codes:
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T.Touzé,
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E.Bokma,
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Interactions underlying assembly of the Escherichia coli AcrAB-TolC multidrug efflux system.
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| |
Mol Cell,
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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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