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* Residue conservation analysis
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PDB id:
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Cytokine
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Title:
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Crystal structure of chemokine domain of fractalkine
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Structure:
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Fractalkine. Chain: a, b, c, d. Fragment: chemokine domain. Synonym: neurotactin, cx3c membrane-anchored chemokine, small inducible cytokine d1. Engineered: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562.
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Biol. unit:
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Octamer (from
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Resolution:
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2.00Å
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R-factor:
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0.237
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R-free:
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0.321
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Authors:
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D.M.Hoover,L.S.Mizoue,T.M.Handel,J.Lubkowski
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Key ref:
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D.M.Hoover
et al.
(2000).
The crystal structure of the chemokine domain of fractalkine shows a novel quaternary arrangement.
J Biol Chem,
275,
23187-23193.
PubMed id:
DOI:
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Date:
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26-May-00
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Release date:
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06-Sep-00
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PROCHECK
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Headers
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References
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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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immune response
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1 term
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Biochemical function
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chemokine activity
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1 term
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DOI no:
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J Biol Chem
275:23187-23193
(2000)
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PubMed id:
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The crystal structure of the chemokine domain of fractalkine shows a novel quaternary arrangement.
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D.M.Hoover,
L.S.Mizoue,
T.M.Handel,
J.Lubkowski.
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ABSTRACT
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Fractalkine, or neurotactin, is a chemokine that is present in endothelial cells
from several tissues, including brain, liver, and kidney. It is the only member
of the CX(3)C class of chemokines. Fractalkine contains a chemokine domain (CDF)
attached to a membrane-spanning domain via a mucin-like stalk. However,
fractalkine can also be proteolytically cleaved from its membrane-spanning
domain to release a freely diffusible form. Fractalkine attracts and immobilizes
leukocytes by binding to its receptor, CX(3)CR1. The x-ray crystal structure of
CDF has been solved and refined to 2.0 A resolution. The CDF monomers form a
dimer through an intermolecular beta-sheet. This interaction is somewhat similar
to that seen in other dimeric CC chemokine crystal structures. However, the
displacement of the first disulfide in CDF causes the dimer to assume a more
compact quaternary structure relative to CC chemokines, which is unique to
CX(3)C chemokines. Although fractalkine can bind to heparin in vitro, as shown
by comparison of electrostatic surface plots with other chemokines and by
heparin chromatography, the role of this property in vivo is not well understood.
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Selected figure(s)
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Figure 2.
Fig. 2. Stereo drawing showing the superposition of CDF
monomers. The monomers are colored as in Fig. 1. The monomers
were superimposed using the program ALIGN (40), with all atoms
included, and the figure was made using the program MOLSCRIPT
(41).
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Figure 3.
Fig. 3. Ribbon drawing of the CDF monomers. Shown here is
a representation of monomer D. Monomer B is nearly identical to
monomer D, whereas monomers A and D differ within residues 5-15.
Also, residues 68-74 are ordered in monomer D producing a
C-terminal extension of the -helix by
1.5 turns (see "Results"). This drawing was made using the
program MOLSCRIPT (41).
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The above figures are
reprinted
by permission from the ASBMB:
J Biol Chem
(2000,
275,
23187-23193)
copyright 2000.
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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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C.L.Salanga,
and
T.M.Handel
(2011).
Chemokine oligomerization and interactions with receptors and glycosaminoglycans: the role of structural dynamics in function.
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Exp Cell Res, 317,
590-601.
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P.Hermand,
F.Pincet,
S.Carvalho,
H.Ansanay,
E.Trinquet,
M.Daoudi,
C.Combadière,
and
P.Deterre
(2008).
Functional adhesiveness of the CX3CL1 chemokine requires its aggregation. Role of the transmembrane domain.
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J Biol Chem, 283,
30225-30234.
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Y.Becker
(2007).
The spreading of HIV-1 infection in the human organism is caused by fractalkine trafficking of the infected lymphocytes--a review, hypothesis and implications for treatment.
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Virus Genes, 34,
93.
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A.Inoue,
H.Hasegawa,
M.Kohno,
M.R.Ito,
M.Terada,
T.Imai,
O.Yoshie,
M.Nose,
and
S.Fujita
(2005).
Antagonist of fractalkine (CX3CL1) delays the initiation and ameliorates the progression of lupus nephritis in MRL/lpr mice.
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Arthritis Rheum, 52,
1522-1533.
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G.J.Swaminathan,
D.E.Holloway,
R.A.Colvin,
G.K.Campanella,
A.C.Papageorgiou,
A.D.Luster,
and
K.R.Acharya
(2003).
Crystal structures of oligomeric forms of the IP-10/CXCL10 chemokine.
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Structure, 11,
521-532.
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PDB codes:
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E.J.Fernandez,
and
E.Lolis
(2002).
Structure, function, and inhibition of chemokines.
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Annu Rev Pharmacol Toxicol, 42,
469-499.
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H.Lortat-Jacob,
A.Grosdidier,
and
A.Imberty
(2002).
Structural diversity of heparan sulfate binding domains in chemokines.
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Proc Natl Acad Sci U S A, 99,
1229-1234.
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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
codes are
shown on the right.
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