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Chemokine (chemoattractant cytokine)
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PDB id
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1don
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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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4 terms
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Biological process
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helper T cell extravasation
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66 terms
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Biochemical function
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receptor binding
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7 terms
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DOI no:
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Biochemistry
35:6569-6584
(1996)
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PubMed id:
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Heteronuclear (1H, 13C, 15N) NMR assignments and solution structure of the monocyte chemoattractant protein-1 (MCP-1) dimer.
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T.M.Handel,
P.J.Domaille.
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ABSTRACT
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A full high-resolution three-dimensional solution structure of the monocyte
chemoattractant protein-1 (MCP-1 or MCAF) homodimer has been determined by
heteronuclear multidimensional NMR. MCP-1 is a member of a family of small
proteins which play a crucial role in immune surveillance by orchestrating the
recruitment of specific leukocytes to areas of immune challenge. The protein was
uniformly isotopically enriched with 13C and 15N by expression in Escherichia
coli, and complete sequence-specific resonance assignments were obtained by a
combination of heteronuclear double- and triple-resonance experiments. The
secondary structure was deduced from characteristic patterns of NOEs, 13 C
alpha/beta chemical shifts, measurements of 3JHNH alpha scalar couplings, and
patterns of slowly exchanging amide protons. Because MCP-1 forms symmetrical
homodimers, additional experiments were carried out to unambiguously establish
the quaternary contacts. NOEs from these novel experiments were merged with more
traditional heteronuclear separated NOE measurements in an iterative strategy to
partition the restraints between explicit inter/intrasubunit contacts and a
class wherein both were retained as ambiguous. With more than 30 restraints per
residue, the three-dimensional structure is well-defined with a backbone rmsd of
0.37 A to the mean over residues 5-69 of the dimer. We compare the structure
with those recently reported for the related chemokines MIP-1 beta and RANTES
and highlight the differences in terms of receptor specificity and function as
well as interpret the known biological activity data of MCP-1 mutants.
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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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J.W.Murphy,
H.Yuan,
Y.Kong,
Y.Xiong,
and
E.J.Lolis
(2010).
Heterologous quaternary structure of CXCL12 and its relationship to the CC chemokine family.
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| |
Proteins, 78,
1331-1337.
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PDB codes:
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T.L.Grygiel,
A.Teplyakov,
G.Obmolova,
N.Stowell,
R.Holland,
J.F.Nemeth,
S.C.Pomerantz,
M.Kruszynski,
and
G.L.Gilliland
(2010).
Synthesis by native chemical ligation and crystal structure of human CCL2.
|
| |
Biopolymers, 94,
350-359.
|
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PDB code:
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E.Melgarejo,
M.A.Medina,
F.Sánchez-Jiménez,
and
J.L.Urdiales
(2009).
Monocyte chemoattractant protein-1: a key mediator in inflammatory processes.
|
| |
Int J Biochem Cell Biol, 41,
998.
|
|
|
|
|
|
|
S.L.Deshmane,
S.Kremlev,
S.Amini,
and
B.E.Sawaya
(2009).
Monocyte chemoattractant protein-1 (MCP-1): an overview.
|
| |
J Interferon Cytokine Res, 29,
313-326.
|
|
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|
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|
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C.Barinka,
A.Prahl,
and
J.Lubkowski
(2008).
Structure of human monocyte chemoattractant protein 4 (MCP-4/CCL13).
|
| |
Acta Crystallogr D Biol Crystallogr, 64,
273-278.
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PDB code:
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I.V.Nesmelova,
Y.Sham,
J.Gao,
and
K.H.Mayo
(2008).
CXC and CC Chemokines Form Mixed Heterodimers: ASSOCIATION FREE ENERGIES FROM MOLECULAR DYNAMICS SIMULATIONS AND EXPERIMENTAL CORRELATIONS.
|
| |
J Biol Chem, 283,
24155-24166.
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H.Jin,
X.Shen,
B.R.Baggett,
X.Kong,
and
P.J.LiWang
(2007).
The human CC chemokine MIP-1beta dimer is not competent to bind to the CCR5 receptor.
|
| |
J Biol Chem, 282,
27976-27983.
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S.J.Allen,
S.E.Crown,
and
T.M.Handel
(2007).
Chemokine: receptor structure, interactions, and antagonism.
|
| |
Annu Rev Immunol, 25,
787-820.
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M.S.Formaneck,
L.Ma,
and
Q.Cui
(2006).
Effects of temperature and salt concentration on the structural stability of human lymphotactin: insights from molecular simulations.
|
| |
J Am Chem Soc, 128,
9506-9517.
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S.E.Crown,
Y.Yu,
M.D.Sweeney,
J.A.Leary,
and
T.M.Handel
(2006).
Heterodimerization of CCR2 chemokines and regulation by glycosaminoglycan binding.
|
| |
J Biol Chem, 281,
25438-25446.
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J.Y.Springael,
E.Urizar,
and
M.Parmentier
(2005).
Dimerization of chemokine receptors and its functional consequences.
|
| |
Cytokine Growth Factor Rev, 16,
611-623.
|
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T.M.Handel,
Z.Johnson,
S.E.Crown,
E.K.Lau,
and
A.E.Proudfoot
(2005).
Regulation of protein function by glycosaminoglycans--as exemplified by chemokines.
|
| |
Annu Rev Biochem, 74,
385-410.
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E.K.Lau,
C.D.Paavola,
Z.Johnson,
J.P.Gaudry,
E.Geretti,
F.Borlat,
A.J.Kungl,
A.E.Proudfoot,
and
T.M.Handel
(2004).
Identification of the glycosaminoglycan binding site of the CC chemokine, MCP-1: implications for structure and function in vivo.
|
| |
J Biol Chem, 279,
22294-22305.
|
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T.Schountz,
R.Green,
B.Davenport,
A.Buniger,
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.
|
| |
BMC Immunol, 5,
1.
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B.T.Seet,
C.A.McCaughan,
T.M.Handel,
A.Mercer,
C.Brunetti,
G.McFadden,
and
S.B.Fleming
(2003).
Analysis of an orf virus chemokine-binding protein: Shifting ligand specificities among a family of poxvirus viroceptors.
|
| |
Proc Natl Acad Sci U S A, 100,
15137-15142.
|
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C.Daly,
and
B.J.Rollins
(2003).
Monocyte chemoattractant protein-1 (CCL2) in inflammatory disease and adaptive immunity: therapeutic opportunities and controversies.
|
| |
Microcirculation, 10,
247-257.
|
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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.
|
| |
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.
|
| |
Annu Rev Pharmacol Toxicol, 42,
469-499.
|
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|
|
E.S.Kuloğlu,
D.R.McCaslin,
J.L.Markley,
and
B.F.Volkman
(2002).
Structural rearrangement of human lymphotactin, a C chemokine, under physiological solution conditions.
|
| |
J Biol Chem, 277,
17863-17870.
|
|
|
|
|
|
|
B.T.Seet,
R.Singh,
C.Paavola,
E.K.Lau,
T.M.Handel,
and
G.McFadden
(2001).
Molecular determinants for CC-chemokine recognition by a poxvirus CC-chemokine inhibitor.
|
| |
Proc Natl Acad Sci U S A, 98,
9008-9013.
|
|
|
|
|
|
|
C.Baysal,
and
A.R.Atilgan
(2001).
Elucidating the structural mechanisms for biological activity of the chemokine family.
|
| |
Proteins, 43,
150-160.
|
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|
|
|
|
C.G.Beck,
C.Studer,
J.F.Zuber,
B.J.Demange,
U.Manning,
and
R.Urfer
(2001).
The viral CC chemokine-binding protein vCCI inhibits monocyte chemoattractant protein-1 activity by masking its CCR2B-binding site.
|
| |
J Biol Chem, 276,
43270-43276.
|
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|
W.Shao,
E.Fernandez,
A.Sachpatzidis,
J.Wilken,
D.A.Thompson,
B.I.Schweitzer,
and
E.Lolis
(2001).
CCR2 and CCR5 receptor-binding properties of herpesvirus-8 vMIP-II based on sequence analysis and its solution structure.
|
| |
Eur J Biochem, 268,
2948-2959.
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PDB code:
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Buyong,
J.Xiong,
J.Lubkowski,
and
R.Nussinov
(2000).
Homology modeling and molecular dynamics simulations of lymphotactin.
|
| |
Protein Sci, 9,
2192-2199.
|
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|
|
J.Blaszczyk,
E.V.Coillie,
P.Proost,
J.V.Damme,
G.Opdenakker,
G.D.Bujacz,
J.M.Wang,
and
X.Ji
(2000).
Complete crystal structure of monocyte chemotactic protein-2, a CC chemokine that interacts with multiple receptors.
|
| |
Biochemistry, 39,
14075-14081.
|
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PDB code:
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J.S.Laurence,
C.Blanpain,
J.W.Burgner,
M.Parmentier,
and
P.J.LiWang
(2000).
CC chemokine MIP-1 beta can function as a monomer and depends on Phe13 for receptor binding.
|
| |
Biochemistry, 39,
3401-3409.
|
|
|
|
|
|
|
K.L.Mayer,
and
M.J.Stone
(2000).
NMR solution structure and receptor peptide binding of the CC chemokine eotaxin-2.
|
| |
Biochemistry, 39,
8382-8395.
|
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PDB codes:
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A.C.LiWang,
J.J.Cao,
H.Zheng,
Z.Lu,
S.C.Peiper,
and
P.J.LiWang
(1999).
Dynamics study on the anti-human immunodeficiency virus chemokine viral macrophage-inflammatory protein-II (VMIP-II) reveals a fully monomeric protein.
|
| |
Biochemistry, 38,
442-453.
|
|
|
|
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|
|
A.C.Liwang,
Z.X.Wang,
Y.Sun,
S.C.Peiper,
and
P.J.Liwang
(1999).
The solution structure of the anti-HIV chemokine vMIP-II.
|
| |
Protein Sci, 8,
2270-2280.
|
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|
PDB code:
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|
E.Van Coillie,
J.Van Damme,
and
G.Opdenakker
(1999).
The MCP/eotaxin subfamily of CC chemokines.
|
| |
Cytokine Growth Factor Rev, 10,
61-86.
|
|
|
|
|
|
|
H.Sticht,
S.E.Escher,
K.Schweimer,
W.G.Forssmann,
P.Rösch,
and
K.Adermann
(1999).
Solution structure of the human CC chemokine 2: A monomeric representative of the CC chemokine subtype.
|
| |
Biochemistry, 38,
5995-6002.
|
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PDB code:
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J.Saunders,
and
C.M.Tarby
(1999).
Opportunities for novel therapeutic agents acting at chemokine receptors.
|
| |
Drug Discov Today, 4,
80-92.
|
|
|
|
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|
|
K.Jarnagin,
D.Grunberger,
M.Mulkins,
B.Wong,
S.Hemmerich,
C.Paavola,
A.Bloom,
S.Bhakta,
F.Diehl,
R.Freedman,
D.McCarley,
I.Polsky,
A.Ping-Tsou,
A.Kosaka,
and
T.M.Handel
(1999).
Identification of surface residues of the monocyte chemotactic protein 1 that affect signaling through the receptor CCR2.
|
| |
Biochemistry, 38,
16167-16177.
|
|
|
|
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|
|
L.S.Mizoue,
J.F.Bazan,
E.C.Johnson,
and
T.M.Handel
(1999).
Solution structure and dynamics of the CX3C chemokine domain of fractalkine and its interaction with an N-terminal fragment of CX3CR1.
|
| |
Biochemistry, 38,
1402-1414.
|
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PDB code:
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C.D.Paavola,
S.Hemmerich,
D.Grunberger,
I.Polsky,
A.Bloom,
R.Freedman,
M.Mulkins,
S.Bhakta,
D.McCarley,
L.Wiesent,
B.Wong,
K.Jarnagin,
and
T.M.Handel
(1998).
Monomeric monocyte chemoattractant protein-1 (MCP-1) binds and activates the MCP-1 receptor CCR2B.
|
| |
J Biol Chem, 273,
33157-33165.
|
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|
|
C.Dealwis,
E.J.Fernandez,
D.A.Thompson,
R.J.Simon,
M.A.Siani,
and
E.Lolis
(1998).
Crystal structure of chemically synthesized [N33A] stromal cell-derived factor 1alpha, a potent ligand for the HIV-1 "fusin" coreceptor.
|
| |
Proc Natl Acad Sci U S A, 95,
6941-6946.
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PDB code:
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J.S.Laurence,
A.C.LiWang,
and
P.J.LiWang
(1998).
Effect of N-terminal truncation and solution conditions on chemokine dimer stability: nuclear magnetic resonance structural analysis of macrophage inflammatory protein 1 beta mutants.
|
| |
Biochemistry, 37,
9346-9354.
|
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M.P.Crump,
K.Rajarathnam,
K.S.Kim,
I.Clark-Lewis,
and
B.D.Sykes
(1998).
Solution structure of eotaxin, a chemokine that selectively recruits eosinophils in allergic inflammation.
|
| |
J Biol Chem, 273,
22471-22479.
|
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PDB codes:
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G.McFadden,
and
D.Kelvin
(1997).
New strategies for chemokine inhibition and modulation: you take the high road and I'll take the low road.
|
| |
Biochem Pharmacol, 54,
1271-1280.
|
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J.Lubkowski,
G.Bujacz,
L.Boqué,
P.J.Domaille,
T.M.Handel,
and
A.Wlodawer
(1997).
The structure of MCP-1 in two crystal forms provides a rare example of variable quaternary interactions.
|
| |
Nat Struct Biol, 4,
64-69.
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PDB codes:
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M.G.Newlon,
M.Roy,
Z.E.Hausken,
J.D.Scott,
and
P.A.Jennings
(1997).
The A-kinase anchoring domain of type IIalpha cAMP-dependent protein kinase is highly helical.
|
| |
J Biol Chem, 272,
23637-23644.
|
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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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Links
