PDBsum entry 1don

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Chemokine (chemoattractant cytokine) PDB id
Protein chain
76 a.a. *
* Residue conservation analysis
PDB id:
Name: Chemokine (chemoattractant cytokine)
Title: Solution structure of the monocyte chemoattractant protein- 1 dimer using heteronuclear, nmr, 20 structures
Structure: Mcp-1. Chain: a, b. Synonym: mcaf. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562.
NMR struc: 20 models
Authors: P.J.Domaille,T.M.Handel
Key ref:
T.M.Handel and P.J.Domaille (1996). Heteronuclear (1H, 13C, 15N) NMR assignments and solution structure of the monocyte chemoattractant protein-1 (MCP-1) dimer. Biochemistry, 35, 6569-6584. PubMed id: 8639605 DOI: 10.1021/bi9602270
21-Jan-96     Release date:   14-Oct-96    
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Protein chains
Pfam   ArchSchema ?
P13500  (CCL2_HUMAN) -  C-C motif chemokine 2
99 a.a.
76 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular region   4 terms 
  Biological process     helper T cell extravasation   71 terms 
  Biochemical function     receptor binding     7 terms  


DOI no: 10.1021/bi9602270 Biochemistry 35:6569-6584 (1996)
PubMed id: 8639605  
Heteronuclear (1H, 13C, 15N) NMR assignments and solution structure of the monocyte chemoattractant protein-1 (MCP-1) dimer.
T.M.Handel, P.J.Domaille.
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.

Literature references that cite this PDB file's key reference

  PubMed id Reference
21223963 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.  
20077567 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.
  Proteins, 78, 1331-1337.
PDB codes: 3gv3 3hp3
20091676 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.
PDB code: 3ifd
18761421 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.  
19441883 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.  
18323622 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: 2ra4
18550532 I.V.Nesmelova, Y.Sham, J.Gao, and K.H.Mayo (2008).
  J Biol Chem, 283, 24155-24166.  
17644519 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.  
17291188 S.J.Allen, S.E.Crown, and T.M.Handel (2007).
Chemokine: receptor structure, interactions, and antagonism.
  Annu Rev Immunol, 25, 787-820.  
16848488 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.  
16803905 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.  
15979374 J.Y.Springael, E.Urizar, and M.Parmentier (2005).
Dimerization of chemokine receptors and its functional consequences.
  Cytokine Growth Factor Rev, 16, 611-623.  
15952892 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.  
15033992 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.  
14720307 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.  
14657392 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.  
12851642 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.  
12737818 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.
PDB codes: 1o7y 1o7z 1o80
11807180 E.J.Fernandez, and E.Lolis (2002).
Structure, function, and inhibition of chemokines.
  Annu Rev Pharmacol Toxicol, 42, 469-499.  
11889129 E.S.Kulo─člu, 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.  
11470923 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.  
11276085 C.Baysal, and A.R.Atilgan (2001).
Elucidating the structural mechanisms for biological activity of the chemokine family.
  Proteins, 43, 150-160.  
11551937 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.  
11358512 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.
PDB code: 1hhv
  11152129 Buyong, J.Xiong, J.Lubkowski, and R.Nussinov (2000).
Homology modeling and molecular dynamics simulations of lymphotactin.
  Protein Sci, 9, 2192-2199.  
11087354 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: 1esr
10727234 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.  
10913244 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: 1eig 1eih
9890927 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.  
  10595530 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: 1vmp
10379912 E.Van Coillie, J.Van Damme, and G.Opdenakker (1999).
The MCP/eotaxin subfamily of CC chemokines.
  Cytokine Growth Factor Rev, 10, 61-86.  
10320325 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: 2hcc
10234160 J.Saunders, and C.M.Tarby (1999).
Opportunities for novel therapeutic agents acting at chemokine receptors.
  Drug Discov Today, 4, 80-92.  
10587439 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.  
9931005 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: 1b2t
9837883 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.  
9618518 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.
PDB code: 1a15
9649315 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.  
9712872 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: 1eot 2eot
9393669 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.  
8989326 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.
PDB codes: 1dok 1dol
9295304 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.  
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.