 |
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
 |
 |
 |
 |
 |
 |
 |
 |
 |
 |
 |
 |
 |
 |
 |
|
|
|
|
|
|
|
|
|
|
Signaling protein
|
PDB id
|
|
|
|
1bo0
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
Contents |
 |
|
|
|
|
|
|
|
* Residue conservation analysis
|
|
|
|
 |
|
 |
|
 |
|
|
Gene Ontology (GO) functional annotation
|
|
|
|
 |
 |
 |
|
 |
 |
 |
 |
|
 |
|
Cellular component
|
extracellular region
|
2 terms
|
 |
|
Biological process
|
immune response
|
6 terms
|
 |
|
Biochemical function
|
cytokine activity
|
4 terms
|
 |
|
|
 |
 |
 |
 |
 |
 |
 |
 |
 |
 |
 |
 |
 |
 |
 |
 |
 |
 |
 |
 |
|
|
|
| |
|
DOI no:
|
FEBS Lett
395:277-282
(1996)
|
|
PubMed id:
|
|
|
|
|
| |
|
Structural characterization of a monomeric chemokine: monocyte chemoattractant protein-3.
|
|
K.S.Kim,
K.Rajarathnam,
I.Clark-Lewis,
B.D.Sykes.
|
|
|
|
| |
ABSTRACT
|
|
|
| |
|
1H-NMR spectroscopy and analytical ultracentrifugation studies reveal that
monocyte chemoattractant protein-3 (MCP-3) is a monomer. NMR solution structure
shows that MCP-3 adopts an alphabeta fold similar to what is observed in
structures of other known chemokines. However, MCP-3 is unique in that it does
not show a propensity to form dimers. The closely related chemokines MCP-1 and
MCP-2 show a monomer-dimer equilibrium in sedimentation equilibrium studies
(approximately 0.2-2 mg/ml). As these proteins are present at nanomolar
concentrations in vivo, the results suggest that they are monomeric at
functional concentrations and that the monomer is the functionally significant
form of MCP-1, MCP-2 and MCP-3.
|
|
|
|
|
| |
Selected figure(s)
|
|
|
| |
 |
 |
|
 |
|
 |
Figure 1.
Fig. 1. lignment of the primary amino acid sequence of MCP-1, MCP-2 and MCP-3. Disulfide bonds between conserved cysteines are indi-
cated.
|
 |
Figure 6.
Fig. 6. Comparison of MCP-3 (thick black) with MIP-113 (thick gray) and monomeric L-8 black). The best-fit superpositions of the bac-
bone atoms are shown.
|
 |
|
|
|
| |
The above figures are
reprinted
by permission from the Federation of European Biochemical Societies:
FEBS Lett
(1996,
395,
277-282)
copyright 1996.
|
|
|
|
 |
 |
|
 |
 |
 |
 |
 |
 |
 |
 |
 |
|
Literature references that cite this PDB file's key reference
|
|
 |
| |
PubMed id
|
 |
Reference
|
 |
|
|
|
 |
C.L.Salanga,
and
T.M.Handel
(2011).
Chemokine oligomerization and interactions with receptors and glycosaminoglycans: the role of structural dynamics in function.
|
| |
Exp Cell Res, 317,
590-601.
|
 |
|
|
|
|
 |
R.R.Koenen,
P.von Hundelshausen,
I.V.Nesmelova,
A.Zernecke,
E.A.Liehn,
A.Sarabi,
B.K.Kramp,
A.M.Piccinini,
S.R.Paludan,
M.A.Kowalska,
A.J.Kungl,
T.M.Hackeng,
K.H.Mayo,
and
C.Weber
(2009).
Disrupting functional interactions between platelet chemokines inhibits atherosclerosis in hyperlipidemic mice.
|
| |
Nat Med, 15,
97.
|
 |
|
|
|
|
 |
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.
|
 |
|
PDB code:
|
 |
|
|
|
|
|
 |
L.Rajagopalan,
and
K.Rajarathnam
(2006).
Structural basis of chemokine receptor function--a model for binding affinity and ligand selectivity.
|
| |
Biosci Rep, 26,
325-339.
|
 |
|
|
|
|
 |
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.
|
 |
|
|
|
|
 |
J.Y.Springael,
E.Urizar,
and
M.Parmentier
(2005).
Dimerization of chemokine receptors and its functional consequences.
|
| |
Cytokine Growth Factor Rev, 16,
611-623.
|
 |
|
|
|
|
 |
Y.Yu,
M.D.Sweeney,
O.M.Saad,
S.E.Crown,
A.R.Hsu,
T.M.Handel,
and
J.A.Leary
(2005).
Chemokine-glycosaminoglycan binding: specificity for CCR2 ligand binding to highly sulfated oligosaccharides using FTICR mass spectrometry.
|
| |
J Biol Chem, 280,
32200-32208.
|
 |
|
|
|
|
 |
V.Petkovic,
C.Moghini,
S.Paoletti,
M.Uguccioni,
and
B.Gerber
(2004).
Eotaxin-3/CCL26 is a natural antagonist for CC chemokine receptors 1 and 5. A human chemokine with a regulatory role.
|
| |
J Biol Chem, 279,
23357-23363.
|
 |
|
|
|
|
 |
A.E.Proudfoot,
T.M.Handel,
Z.Johnson,
E.K.Lau,
P.LiWang,
I.Clark-Lewis,
F.Borlat,
T.N.Wells,
and
M.H.Kosco-Vilbois
(2003).
Glycosaminoglycan binding and oligomerization are essential for the in vivo activity of certain chemokines.
|
| |
Proc Natl Acad Sci U S A, 100,
1885-1890.
|
 |
|
|
|
|
 |
E.J.Fernandez,
and
E.Lolis
(2002).
Structure, function, and inhibition of chemokines.
|
| |
Annu Rev Pharmacol Toxicol, 42,
469-499.
|
 |
|
|
|
|
 |
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.
|
 |
|
|
|
|
 |
Buyong,
J.Xiong,
J.Lubkowski,
and
R.Nussinov
(2000).
Homology modeling and molecular dynamics simulations of lymphotactin.
|
| |
Protein Sci, 9,
2192-2199.
|
 |
|
|
|
|
 |
E.J.Fernandez,
J.Wilken,
D.A.Thompson,
S.C.Peiper,
and
E.Lolis
(2000).
Comparison of the structure of vMIP-II with eotaxin-1, RANTES, and MCP-3 suggests a unique mechanism for CCR3 activation.
|
| |
Biochemistry, 39,
12837-12844.
|
 |
|
PDB code:
|
 |
|
|
|
|
|
 |
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.
|
 |
|
PDB code:
|
 |
|
|
|
|
|
 |
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.
|
 |
|
PDB codes:
|
 |
|
|
|
|
|
 |
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.
|
 |
|
|
|
|
 |
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.
|
 |
|
PDB code:
|
 |
|
|
|
|
|
 |
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.
|
 |
|
PDB code:
|
 |
|
|
|
|
|
 |
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.
|
 |
|
PDB code:
|
 |
|
|
|
|
|
 |
M.P.Crump,
L.Spyracopoulos,
P.Lavigne,
K.S.Kim,
I.Clark-lewis,
and
B.D.Sykes
(1999).
Backbone dynamics of the human CC chemokine eotaxin: fast motions, slow motions, and implications for receptor binding.
|
| |
Protein Sci, 8,
2041-2054.
|
 |
|
|
|
|
 |
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.
|
 |
|
|
|
|
 |
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.
|
 |
|
|
|
|
 |
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.
|
 |
|
PDB codes:
|
 |
|
|
|
|
|
 |
W.Shao,
L.F.Jerva,
J.West,
E.Lolis,
and
B.I.Schweitzer
(1998).
Solution structure of murine macrophage inflammatory protein-2.
|
| |
Biochemistry, 37,
8303-8313.
|
 |
|
PDB code:
|
 |
|
|
|
|
|
 |
S.Meunier,
J.M.Bernassau,
J.C.Guillemot,
P.Ferrara,
and
H.Darbon
(1997).
Determination of the three-dimensional structure of CC chemokine monocyte chemoattractant protein 3 by 1H two-dimensional NMR spectroscopy.
|
| |
Biochemistry, 36,
4412-4422.
|
 |
|
PDB code:
|
 |
|
|
 |
 |
|
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.
|
|