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Chemoattractant PDB id
1dok
Jmol
Contents
Protein chains
72 a.a. *
Ligands
SO4 ×2
Waters ×116
* Residue conservation analysis
PDB id:
1dok
Name: Chemoattractant
Title: Monocyte chemoattractant protein 1, p-form
Structure: Monocyte chemoattractant protein 1. Chain: a, b. Synonym: mcp-1, mcaf. Engineered: yes. Mutation: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Tetramer (from PQS)
Resolution:
1.85Å     R-factor:   0.191     R-free:   0.245
Authors: J.Lubkowski,G.Bujacz,L.Boque,A.Wlodawer,P.J.Domaille, T.M.Handel
Key ref: J.Lubkowski et al. (1997). The structure of MCP-1 in two crystal forms provides a rare example of variable quaternary interactions. Nat Struct Biol, 4, 64-69. PubMed id: 8989326 DOI: 10.1038/nsb0197-64
Date:
27-Nov-96     Release date:   12-Mar-97    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P13500  (CCL2_HUMAN) -  C-C motif chemokine 2
Seq:
Struc: 		99 a.a.
72 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular region   4 terms 
  Biological process     helper T cell extravasation   66 terms 
  Biochemical function     receptor binding     7 terms  

 

 
DOI no: 10.1038/nsb0197-64 Nat Struct Biol 4:64-69 (1997)
PubMed id: 8989326  
 
 
The structure of MCP-1 in two crystal forms provides a rare example of variable quaternary interactions.
J.Lubkowski, G.Bujacz, L.Boqué, P.J.Domaille, T.M.Handel, A.Wlodawer.
 
  ABSTRACT  
 
The X-ray crystal structure of recombinant human monocyte chemoattractant protein (MCP-1) has been solved in two crystal forms. One crystal form (P), refined to 1.85 A resolution, contains a dimer in the asymmetric unit, while the other (I) contains a monomer and was refined at 2.4 A. Although both crystal forms grow together in the same droplet, the respective quaternary structures of the protein differ dramatically. In addition, both X-ray structures differ to a similar extent from the solution structure of MCP-1. Such extent of variability of quaternary structures is unprecedented. In the crystal structures, the well-ordered N termini of MCP-1 form 3(10)-helices. Comparison of the three MCP-1 structures revealed a direct correlation between the main-chain conformation of the first two cysteine residues and the quaternary arrangements. These data can be used to explain the structural basis for the assignment of residues responsible for biological activity.
 

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.
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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
  20160907 M.R.Schenauer, and J.A.Leary (2009).
An Ion Mobility-Mass Spectrometry Investigation of Monocyte Chemoattractant Protein-1.
  Int J Mass Spectrom, 287, 70-76.  
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
18070938 J.M.Alexander-Brett, and D.H.Fremont (2007).
Dual GPCR and GAG mimicry by the M3 chemokine decoy receptor.
  J Exp Med, 204, 3157-3172.
PDB codes: 2nyz 2nz1
17291188 S.J.Allen, S.E.Crown, and T.M.Handel (2007).
Chemokine: receptor structure, interactions, and antagonism.
  Annu Rev Immunol, 25, 787-820.  
17243149 Y.Li, D.Liu, R.Cao, S.Kumar, C.Dong, J.An, S.R.Wilson, Y.G.Gao, and Z.Huang (2007).
Crystal structure of chemically synthesized vMIP-II.
  Proteins, 67, 243-246.
PDB codes: 2fht 2fj2
  16785103 B.R.Singh (2006).
Botulinum neurotoxin structure, engineering, and novel cellular trafficking and targeting.
  Neurotox Res, 9, 73-92.  
16923346 J.J.Wey, S.S.Tang, and T.Y.Wu (2006).
Disulfide bond reduction corresponds to dimerization and hydrophobi-city changes of Clostridium botulinum type A neurotoxin.
  Acta Pharmacol Sin, 27, 1238-1246.  
16735126 M.D.Sweeney, Y.Yu, and J.A.Leary (2006).
Effects of sulfate position on heparin octasaccharide binding to CCL2 examined by tandem mass spectrometry.
  J Am Soc Mass Spectrom, 17, 1114-1119.  
15942931 M.Kruszynski, N.Stowell, A.Das, J.Seideman, P.Tsui, M.Brigham-Burke, J.F.Nemeth, R.Sweet, and G.A.Heavner (2006).
Synthesis and biological characterization of human monocyte chemoattractant protein 1 (MCP-1) and its analogs.
  J Pept Sci, 12, 25-32.  
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.  
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.  
15990353 Z.Johnson, A.E.Proudfoot, and T.M.Handel (2005).
Interaction of chemokines and glycosaminoglycans: a new twist in the regulation of chemokine function with opportunities for therapeutic intervention.
  Cytokine Growth Factor Rev, 16, 625-636.  
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.  
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
12149255 D.M.Hoover, C.Boulegue, D.Yang, J.J.Oppenheim, K.Tucker, W.Lu, and J.Lubkowski (2002).
The structure of human macrophage inflammatory protein-3alpha /CCL20. Linking antimicrobial and CC chemokine receptor-6-binding activities with human beta-defensins.
  J Biol Chem, 277, 37647-37654.
PDB code: 1m8a
11807180 E.J.Fernandez, and E.Lolis (2002).
Structure, function, and inhibition of chemokines.
  Annu Rev Pharmacol Toxicol, 42, 469-499.  
11889129 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.  
11830659 H.Lortat-Jacob, A.Grosdidier, and A.Imberty (2002).
Structural diversity of heparan sulfate binding domains in chemokines.
  Proc Natl Acad Sci U S A, 99, 1229-1234.  
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.  
11532941 R.A.Staniforth, S.Giannini, L.D.Higgins, M.J.Conroy, A.M.Hounslow, R.Jerala, C.J.Craven, and J.P.Waltho (2001).
Three-dimensional domain swapping in the folded and molten-globule states of cystatins, an amyloid-forming structural superfamily.
  EMBO J, 20, 4774-4781.
PDB code: 1n9j
11559700 R.Martinelli, I.Sabroe, G.LaRosa, T.J.Williams, and J.E.Pease (2001).
The CC chemokine eotaxin (CCL11) is a partial agonist of CC chemokine receptor 2b.
  J Biol Chem, 276, 42957-42964.  
11294637 S.Cai, and B.R.Singh (2001).
A correlation between differential structural features and the degree of endopeptidase activity of type A botulinum neurotoxin in aqueous solution.
  Biochemistry, 40, 4693-4702.  
  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.  
  11106181 J.T.Ashfield, T.Meyers, D.Lowne, P.G.Varley, J.R.Arnold, P.Tan, J.C.Yang, L.G.Czaplewski, T.Dudgeon, and J.Fisher (2000).
Chemical modification of a variant of human MIP-1alpha; implications for dimer structure.
  Protein Sci, 9, 2047-2053.  
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
  11080645 Y.W.Chen, E.J.Dodson, and G.J.Kleywegt (2000).
Does NMR mean "not for molecular replacement"? Using NMR-based search models to solve protein crystal structures.
  Structure, 8, R213-R220.  
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.  
  10400729 A.Trkola, C.Gordon, J.Matthews, E.Maxwell, T.Ketas, L.Czaplewski, A.E.Proudfoot, and J.P.Moore (1999).
The CC-chemokine RANTES increases the attachment of human immunodeficiency virus type 1 to target cells via glycosaminoglycans and also activates a signal transduction pathway that enhances viral infectivity.
  J Virol, 73, 6370-6379.  
  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
9889151 J.Wilken, D.Hoover, D.A.Thompson, P.N.Barlow, H.McSparron, L.Picard, A.Wlodawer, J.Lubkowski, and S.B.Kent (1999).
Total chemical synthesis and high-resolution crystal structure of the potent anti-HIV protein AOP-RANTES.
  Chem Biol, 6, 43-51.
PDB code: 1b3a
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.  
10347159 L.G.Czaplewski, J.McKeating, C.J.Craven, L.D.Higgins, V.Appay, A.Brown, T.Dudgeon, L.A.Howard, T.Meyers, J.Owen, S.R.Palan, P.Tan, G.Wilson, N.R.Woods, C.M.Heyworth, B.I.Lord, D.Brotherton, R.Christison, S.Craig, S.Cribbes, R.M.Edwards, S.J.Evans, R.Gilbert, P.Morgan, E.Randle, N.Schofield, P.G.Varley, J.Fisher, J.P.Waltho, and M.G.Hunter (1999).
Identification of amino acid residues critical for aggregation of human CC chemokines macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, and RANTES. Characterization of active disaggregated chemokine variants.
  J Biol Chem, 274, 16077-16084.
PDB codes: 1b50 1b53
  10548050 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.  
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.  
9461080 J.Lubkowski, F.Hennecke, A.Plückthun, and A.Wlodawer (1998).
The structural basis of phage display elucidated by the crystal structure of the N-terminal domains of g3p.
  Nat Struct Biol, 5, 140-147.
PDB code: 1g3p
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.  
9792674 L.Chakravarty, L.Rogers, T.Quach, S.Breckenridge, and P.E.Kolattukudy (1998).
Lysine 58 and histidine 66 at the C-terminal alpha-helix of monocyte chemoattractant protein-1 are essential for glycosaminoglycan binding.
  J Biol Chem, 273, 29641-29647.  
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
  9739086 P.R.Pokkuluri, D.B.Huang, R.Raffen, X.Cai, G.Johnson, P.W.Stevens, F.J.Stevens, and M.Schiffer (1998).
A domain flip as a result of a single amino-acid substitution.
  Structure, 6, 1067-1073.
PDB codes: 2lve 3lve 4lve
9622482 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: 1mi2
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.