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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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2 terms
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Biological process
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positive regulation of podosome assembly
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16 terms
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Biochemical function
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protein binding
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4 terms
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DOI no:
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J Mol Biol
224:1075-1085
(1992)
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PubMed id:
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Three-dimensional structure of recombinant human granulocyte-macrophage colony-stimulating factor.
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M.R.Walter,
W.J.Cook,
S.E.Ealick,
T.L.Nagabhushan,
P.P.Trotta,
C.E.Bugg.
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ABSTRACT
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The crystal structure of recombinant human granulocyte-macrophage
colony-stimulating factor (rhGM-CSF) has been determined at 2.8 A resolution
using multiple isomorphous replacement techniques. There are two molecules in
the crystallographic asymmetric unit, which are related by an approximate
non-crystallographic 2-fold axis. The overall structure is highly compact and
globular with a predominantly hydrophobic core. The main structural feature of
rhGM-CSF is a four alpha-helix bundle, which represents approximately 42% of the
structure. The helices are arranged in a left-handed antiparallel bundle with
two overhand connections. Within the connections is a two-stranded antiparallel
beta-sheet. The tertiary structure of rhGM-CSF has a topology similar to that of
porcine growth factor and interferon-beta. Most of the proposed critical regions
for receptor binding are located on a continuous surface at one end of the
molecule that includes the C terminus.
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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.Mirza,
A.Walker,
J.Chen,
J.M.Murphy,
and
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(2010).
The Ig-like domain of human GM-CSF receptor alpha plays a critical role in cytokine binding and receptor activation.
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Biochem J, 426,
307-317.
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D.L.Lee,
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(2008).
Preparation and characterization of monopegylated human granulocyte-macrophage colony-stimulating factor.
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J Interferon Cytokine Res, 28,
101-112.
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A.Sebollela,
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(2005).
Heparin-binding sites in granulocyte-macrophage colony-stimulating factor. Localization and regulation by histidine ionization.
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J Biol Chem, 280,
31949-31956.
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D.H.Doherty,
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J.M.Hughes,
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and
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(2005).
Site-specific PEGylation of engineered cysteine analogues of recombinant human granulocyte-macrophage colony-stimulating factor.
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Bioconjug Chem, 16,
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Generation of competent bone marrow-derived antigen presenting cells from the deer mouse (Peromyscus maniculatus).
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BMC Immunol, 5,
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R.Chiarini,
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and
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(2004).
Identification of an antigenic domain near the C terminus of human granulocyte-macrophage colony-stimulating factor and its spatial localization.
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J Biol Chem, 279,
37908-37917.
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S.Avery,
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(2004).
Characterization of the first nonmammalian T2 cytokine gene cluster: the cluster contains functional single-copy genes for IL-3, IL-4, IL-13, and GM-CSF, a gene for IL-5 that appears to be a pseudogene, and a gene encoding another cytokinelike transcript, KK34.
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J Interferon Cytokine Res, 24,
600-610.
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T.Schountz,
R.Green,
B.Davenport,
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T.Richens,
J.J.Root,
F.Davidson,
C.H.Calisher,
and
B.J.Beaty
(2004).
Cloning and characterization of deer mouse (Peromyscus maniculatus) cytokine and chemokine cDNAs.
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BMC Immunol, 5,
1.
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G.Serini,
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and
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(2003).
Modeling the early stages of vascular network assembly.
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EMBO J, 22,
1771-1779.
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A.V.Zavialov,
N.V.Batchikova,
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L.E.Petrovskaya,
V.G.Korobko,
J.Kersley,
S.MacIntyre,
and
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(2001).
Secretion of recombinant proteins via the chaperone/usher pathway in Escherichia coli.
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Appl Environ Microbiol, 67,
1805-1814.
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A.Tsarbopoulos,
J.Varnerin,
S.Cannon-Carlson,
D.Wylie,
B.Pramanik,
J.Tang,
and
T.L.Nagabhushan
(2000).
Mass spectrometric mapping of disulfide bonds in recombinant human interleukin-13.
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J Mass Spectrom, 35,
446-453.
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L.Cosenza,
A.Rosenbach,
J.V.White,
J.R.Murphy,
and
T.Smith
(2000).
Comparative model building of interleukin-7 using interleukin-4 as a template: a structural hypothesis that displays atypical surface chemistry in helix D important for receptor activation.
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Protein Sci, 9,
916-926.
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R.P.Revoltella,
L.Laricchia Robbio,
T.Vikinge,
E.Pardi,
E.Levantini,
and
P.Beffy
(1999).
Human GM-CSF interaction with the alpha-chain of its receptor studied using surface plasmon resonance.
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Biosens Bioelectron, 14,
555-567.
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R.J.Simpson,
A.Hammacher,
D.K.Smith,
J.M.Matthews,
and
L.D.Ward
(1997).
Interleukin-6: structure-function relationships.
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Protein Sci, 6,
929-955.
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S.Fiori,
S.Mammi,
E.Peggion,
P.Rovero,
S.Pegoraro,
and
R.P.Revoltella
(1997).
Conformation of four peptides corresponding to the alpha-helical segments of human GM-CSF.
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J Pept Sci, 3,
336-346.
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T.Li,
T.Horan,
T.Osslund,
G.Stearns,
and
T.Arakawa
(1997).
Conformational changes in G-CSF/Receptor complex as investigated by isotope-edited FTIR spectroscopy.
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Biochemistry, 36,
8849-8857.
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C.Monfardini,
T.Kieber-Emmons,
D.Voet,
A.P.Godillot,
D.B.Weiner,
and
W.V.Williams
(1996).
Rational design of granulocyte-macrophage colony-stimulating factor antagonist peptides.
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J Biol Chem, 271,
2966-2971.
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D.A.Rozwarski,
K.Diederichs,
R.Hecht,
T.Boone,
and
P.A.Karplus
(1996).
Refined crystal structure and mutagenesis of human granulocyte-macrophage colony-stimulating factor.
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Proteins, 26,
304-313.
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PDB code:
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L.Laricchia-Robbio,
B.Liedberg,
T.Platou-Vikinge,
P.Rovero,
P.Beffy,
and
R.P.Revoltella
(1996).
Mapping of monoclonal antibody- and receptor-binding domains on human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) using a surface plasmon resonance-based biosensor.
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Hybridoma, 15,
343-350.
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R.C.Hoffman,
H.Andersen,
K.Walker,
J.D.Krakover,
S.Patel,
M.R.Stamm,
and
S.G.Osborn
(1996).
Peptide, disulfide, and glycosylation mapping of recombinant human thrombopoietin from ser1 to Arg246.
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Biochemistry, 35,
14849-14861.
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A.Gustchina,
A.Zdanov,
C.Schalk-Hihi,
and
A.Wlodawer
(1995).
A model of the complex between interleukin-4 and its receptors.
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Proteins, 21,
140-148.
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PDB code:
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M.J.Czupryn,
J.M.McCoy,
and
H.A.Scoble
(1995).
Structure-function relationships in human interleukin-11. Identification of regions involved in activity by chemical modification and site-directed mutagenesis.
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J Biol Chem, 270,
978-985.
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P.D.Lyne,
P.Bamborough,
D.Duncan,
and
W.G.Richards
(1995).
Molecular modeling of the GM-CSF and IL-3 receptor complexes.
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Protein Sci, 4,
2223-2233.
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D.A.Rozwarski,
A.M.Gronenborn,
G.M.Clore,
J.F.Bazan,
A.Bohm,
A.Wlodawer,
M.Hatada,
and
P.A.Karplus
(1994).
Structural comparisons among the short-chain helical cytokines.
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Structure, 2,
159-173.
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J.M.Von Feldt,
C.Monfardini,
T.Kieber-Emmons,
D.Voet,
D.B.Weiner,
and
W.V.Williams
(1994).
Granulocyte-macrophage colony-stimulating factor mimicry and receptor interactions.
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Immunol Res, 13,
96.
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A.Tsarbopoulos,
B.N.Pramanik,
J.E.Labdon,
P.Reichert,
G.Gitlin,
S.Patel,
V.Sardana,
T.L.Nagabhushan,
and
P.P.Trotta
(1993).
Isolation and characterization of a resistant core peptide of recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF); confirmation of the GM-CSF amino acid sequence by mass spectrometry.
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Protein Sci, 2,
1948-1958.
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A.Wlodawer,
A.Pavlovsky,
and
A.Gustchina
(1993).
Hematopoietic cytokines: similarities and differences in the structures, with implications for receptor binding.
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Protein Sci, 2,
1373-1382.
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C.P.Hill,
T.D.Osslund,
and
D.Eisenberg
(1993).
The structure of granulocyte-colony-stimulating factor and its relationship to other growth factors.
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Proc Natl Acad Sci U S A, 90,
5167-5171.
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PDB code:
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N.J.Murgolo,
W.T.Windsor,
A.Hruza,
P.Reichert,
A.Tsarbopoulos,
S.Baldwin,
E.Huang,
B.Pramanik,
S.Ealick,
and
P.P.Trotta
(1993).
A homology model of human interferon alpha-2.
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Proteins, 17,
62-74.
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PDB codes:
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N.Kruse,
B.J.Shen,
S.Arnold,
H.P.Tony,
T.Müller,
and
W.Sebald
(1993).
Two distinct functional sites of human interleukin 4 are identified by variants impaired in either receptor binding or receptor activation.
|
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EMBO J, 12,
5121-5129.
|
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Y.Mitsui,
T.Senda,
T.Shimazu,
S.Matsuda,
and
J.Utsumi
(1993).
Structural, functional and evolutionary implications of the three-dimensional crystal structure of murine interferon-beta.
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Pharmacol Ther, 58,
93.
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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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