spacer
spacer
Go to PDB code: 
protein Protein-protein interface(s) links
Cytokine(chemotactic) PDB id
1hum
Jmol
Contents
Protein chains
69 a.a. *
Waters ×12
* Residue conservation analysis
PDB id:
1hum
Name: Cytokine(chemotactic)
Title: Solution structure of the chemokine hmip-1beta(slash)act-2 by multi-dimensional nmr: a novel chemokine dimer
Structure: Human macrophage inflammatory protein 1 beta. Chain: a, b. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606
NMR struc: 1 models
Authors: G.M.Clore,P.J.Lodi,D.S.Garrett,A.M.Gronenborn
Key ref: P.J.Lodi et al. (1994). High-resolution solution structure of the beta chemokine hMIP-1 beta by multidimensional NMR. Science, 263, 1762-1767. PubMed id: 8134838 DOI: 10.1126/science.8134838
Date:
31-Jan-94     Release date:   30-Apr-94    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P13236  (CCL4_HUMAN) -  C-C motif chemokine 4
Seq:
Struc: 		92 a.a.
69 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular region   2 terms 
  Biological process     immune response   10 terms 
  Biochemical function     cytokine activity     3 terms  

 

 
DOI no: 10.1126/science.8134838 Science 263:1762-1767 (1994)
PubMed id: 8134838  
 
 
High-resolution solution structure of the beta chemokine hMIP-1 beta by multidimensional NMR.
P.J.Lodi, D.S.Garrett, J.Kuszewski, M.L.Tsang, J.A.Weatherbee, W.J.Leonard, A.M.Gronenborn, G.M.Clore.
 
  ABSTRACT  
 
The three-dimensional structure of a member of the beta subfamily of chemokines, human macrophage inflammatory protein-1 beta (hMIP-1 beta), has been determined with the use of solution multidimensional heteronuclear magnetic resonance spectroscopy. Human MIP-1 beta is a symmetric homodimer with a relative molecular mass of approximately 16 kilodaltons. The structure of the hMIP-1 beta monomer is similar to that of the related alpha chemokine interleukin-8 (IL-8). However, the quaternary structures of the two proteins are entirely distinct, and the dimer interface is formed by a completely different set of residues. Whereas the IL-8 dimer is globular, the hMIP-1 beta dimer is elongated and cylindrical. This provides a rational explanation for the absence of cross-binding and reactivity between the alpha and beta chemokine subfamilies. Calculation of the solvation free energies of dimerization suggests that the formation and stabilization of the two different types of dimers arise from the burial of hydrophobic residues.
 

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.  
21264298 O.Chertov, N.Zhang, X.Chen, J.J.Oppenheim, J.Lubkowski, C.McGrath, R.C.Sowder, B.J.Crise, A.Malyguine, M.A.Kutzler, A.D.Steele, E.E.Henderson, and T.J.Rogers (2011).
Novel peptides based on HIV-1 gp120 sequence with homology to chemokines inhibit HIV infection in cell culture.
  PLoS One, 6, e14474.  
21466412 Y.S.Kang, J.J.Cha, Y.Y.Hyun, and D.R.Cha (2011).
Novel C-C chemokine receptor 2 antagonists in metabolic disease: a review of recent developments.
  Expert Opin Investig Drugs, 20, 745-756.  
20459756 K.J.Metzger, and M.A.Thomas (2010).
Evidence of positive selection at codon sites localized in extracellular domains of mammalian CC motif chemokine receptor proteins.
  BMC Evol Biol, 10, 139.  
20959807 M.Ren, Q.Guo, L.Guo, M.Lenz, F.Qian, R.R.Koenen, H.Xu, A.B.Schilling, C.Weber, R.D.Ye, A.R.Dinner, and W.J.Tang (2010).
Polymerization of MIP-1 chemokine (CCL3 and CCL4) and clearance of MIP-1 by insulin-degrading enzyme.
  EMBO J, 29, 3952-3966.
PDB codes: 2x69 2x6g 2x6l
20659124 R.Colobran, E.Pedrosa, L.Carretero-Iglesia, and M.Juan (2010).
Copy number variation in chemokine superfamily: the complex scene of CCL3L-CCL4L genes in health and disease.
  Clin Exp Immunol, 162, 41-52.  
20668677 S.T.Das, L.Rajagopalan, A.Guerrero-Plata, J.Sai, A.Richmond, R.P.Garofalo, and K.Rajarathnam (2010).
Monomeric and dimeric CXCL8 are both essential for in vivo neutrophil recruitment.
  PLoS One, 5, e11754.  
18317356 E.Viey, C.Lucas, F.Romagne, B.Escudier, S.Chouaib, and A.Caignard (2008).
Chemokine receptors expression and migration potential of tumor-infiltrating and peripheral-expanded Vgamma9Vdelta2 T cells from renal cell carcinoma patients.
  J Immunother, 31, 313-323.  
  19084927 J.R.Larrubia, S.Benito-Martínez, M.Calvino, E.Sanz-de-Villalobos, and T.Parra-Cid (2008).
Role of chemokines and their receptors in viral persistence and liver damage during chronic hepatitis C virus infection.
  World J Gastroenterol, 14, 7149-7159.  
18243436 L.Vangelista, M.Secchi, and P.Lusso (2008).
Rational design of novel HIV-1 entry inhibitors by RANTES engineering.
  Vaccine, 26, 3008-3015.  
18560148 T.Jabeen, P.Leonard, H.Jamaluddin, and K.R.Acharya (2008).
Structure of mouse IP-10, a chemokine.
  Acta Crystallogr D Biol Crystallogr, 64, 611-619.
PDB code: 2r3z
17291188 S.J.Allen, S.E.Crown, and T.M.Handel (2007).
Chemokine: receptor structure, interactions, and antagonism.
  Annu Rev Immunol, 25, 787-820.  
17105719 S.Kim, J.Tsai, I.Kagiampakis, P.LiWang, and M.Vannucci (2007).
Detecting protein dissimilarities in multiple alignments using Bayesian variable selection.
  Bioinformatics, 23, 245-246.  
17411375 T.Cardozo, T.Kimura, S.Philpott, B.Weiser, H.Burger, and S.Zolla-Pazner (2007).
Structural basis for coreceptor selectivity by the HIV type 1 V3 loop.
  AIDS Res Hum Retroviruses, 23, 415-426.  
17024562 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.  
16963564 L.Zhang, M.Derider, M.A.McCornack, S.C.Jao, N.Isern, T.Ness, R.Moyer, and P.J.LiWang (2006).
Solution structure of the complex between poxvirus-encoded CC chemokine inhibitor vCCI and human MIP-1beta.
  Proc Natl Acad Sci U S A, 103, 13985-13990.
PDB codes: 2ffk 2fin
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.  
16005254 K.Princen, and D.Schols (2005).
HIV chemokine receptor inhibitors as novel anti-HIV drugs.
  Cytokine Growth Factor Rev, 16, 659-677.  
14997562 A.Bhaduri, R.Ravishankar, and R.Sowdhamini (2004).
Conserved spatially interacting motifs of protein superfamilies: application to fold recognition and function annotation of genome data.
  Proteins, 54, 657-670.  
12832759 O.A.Asojo, C.Boulègue, D.M.Hoover, W.Lu, and J.Lubkowski (2003).
Structures of thymus and activation-regulated chemokine (TARC).
  Acta Crystallogr D Biol Crystallogr, 59, 1165-1173.
PDB codes: 1nr2 1nr4
11807180 E.J.Fernandez, and E.Lolis (2002).
Structure, function, and inhibition of chemokines.
  Annu Rev Pharmacol Toxicol, 42, 469-499.  
12120410 M.K.Schwarz, and T.N.Wells (2002).
New therapeutics that modulate chemokine networks.
  Nat Rev Drug Discov, 1, 347-358.  
  12401480 P.Menten, A.Wuyts, and J.Van Damme (2002).
Macrophage inflammatory protein-1.
  Cytokine Growth Factor Rev, 13, 455-481.  
11276085 C.Baysal, and A.R.Atilgan (2001).
Elucidating the structural mechanisms for biological activity of the chemokine family.
  Proteins, 43, 150-160.  
11276368 M.Crow, D.D.Taub, S.Cooper, H.E.Broxmeyer, and A.H.Sarris (2001).
Human recombinant interferon-inducible protein-10: intact disulfide bridges are not required for inhibition of hematopoietic progenitors and chemotaxis of T lymphocytes and monocytes.
  J Hematother Stem Cell Res, 10, 147-156.  
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.  
  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.  
10835359 K.Huang, J.M.Louis, L.Donaldson, F.L.Lim, A.D.Sharrocks, and G.M.Clore (2000).
Solution structure of the MEF2A-DNA complex: structural basis for the modulation of DNA bending and specificity by MADS-box transcription factors.
  EMBO J, 19, 2615-2628.
PDB code: 1c7u
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
10491096 A.Lala, M.Gwinn, and E.De Nardin (1999).
Human formyl peptide receptor function role of conserved and nonconserved charged residues.
  Eur J Biochem, 264, 495-499.  
  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
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
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.  
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
9048206 B.J.Doranz, J.F.Berson, J.Rucker, and R.W.Doms (1997).
Chemokine receptors as fusion cofactors for human immunodeficiency virus type 1 (HIV-1).
  Immunol Res, 16, 15-28.  
9346309 F.Coulin, C.A.Power, S.Alouani, M.C.Peitsch, J.M.Schroeder, M.Moshizuki, I.Clark-Lewis, and T.N.Wells (1997).
Characterisation of macrophage inflammatory protein-5/human CC cytokine-2, a member of the macrophage-inflammatory-protein family of chemokines.
  Eur J Biochem, 248, 507-515.  
9405641 H.Arai, C.L.Tsou, and I.F.Charo (1997).
Chemotaxis in a lymphocyte cell line transfected with C-C chemokine receptor 2B: evidence that directed migration is mediated by betagamma dimers released by activation of Galphai-coupled receptors.
  Proc Natl Acad Sci U S A, 94, 14495-14499.  
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
  9260277 L.F.Jerva, G.Sullivan, and E.Lolis (1997).
Functional and receptor binding characterization of recombinant murine macrophage inflammatory protein 2: sequence analysis and mutagenesis identify receptor binding epitopes.
  Protein Sci, 6, 1643-1652.  
9143704 M.Baggiolini, B.Dewald, and B.Moser (1997).
Human chemokines: an update.
  Annu Rev Immunol, 15, 675-705.  
9109648 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: 1ncv
  9070443 S.R.Leong, H.B.Lowman, J.Liu, S.Shire, L.E.Deforge, B.L.Gillece-Castro, R.McDowell, and C.A.Hébert (1997).
IL-8 single-chain homodimers and heterodimers: interactions with chemokine receptors CXCR1, CXCR2, and DARC.
  Protein Sci, 6, 609-617.  
  8740525 C.J.Tsai, S.L.Lin, H.J.Wolfson, and R.Nussinov (1996).
Protein-protein interfaces: architectures and interactions in protein-protein interfaces and in protein cores. Their similarities and differences.
  Crit Rev Biochem Mol Biol, 31, 127-152.  
  8978677 G.J.Graham, P.C.Wilkinson, R.J.Nibbs, S.Lowe, S.O.Kolset, A.Parker, M.G.Freshney, M.L.Tsang, and I.B.Pragnell (1996).
Uncoupling of stem cell inhibition from monocyte chemoattraction in MIP-1alpha by mutagenesis of the proteoglycan binding site.
  EMBO J, 15, 6506-6515.  
  8758187 R.P.Negus (1996).
The chemokines: cytokines that direct leukocyte migration.
  J R Soc Med, 89, 312-314.  
8639605 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.
PDB codes: 1dom 1don
7790818 A.D.Luster, S.M.Greenberg, and P.Leder (1995).
The IP-10 chemokine binds to a specific cell surface heparan sulfate site shared with platelet factor 4 and inhibits endothelial cell proliferation.
  J Exp Med, 182, 219-231.  
  8575189 A.M.Gronenborn, and G.M.Clore (1995).
Structures of protein complexes by multidimensional heteronuclear magnetic resonance spectroscopy.
  Crit Rev Biochem Mol Biol, 30, 351-385.  
7796267 G.M.Clore, J.Ernst, R.Clubb, J.G.Omichinski, W.M.Kennedy, K.Sakaguchi, E.Appella, and A.M.Gronenborn (1995).
Refined solution structure of the oligomerization domain of the tumour suppressor p53.
  Nat Struct Biol, 2, 321-333.
PDB codes: 1sae 1saf 1sag 1sah 1sai 1saj 1sak 1sal
7836918 J.H.Gong, and I.Clark-Lewis (1995).
Antagonists of monocyte chemoattractant protein 1 identified by modification of functionally critical NH2-terminal residues.
  J Exp Med, 181, 631-640.  
  7788295 J.Qin, G.M.Clore, W.M.Kennedy, J.R.Huth, and A.M.Gronenborn (1995).
Solution structure of human thioredoxin in a mixed disulfide intermediate complex with its target peptide from the transcription factor NF kappa B.
  Structure, 3, 289-297.
PDB codes: 1mdi 1mdj 1mdk
  8590003 T.E.Strzelecka, G.M.Clore, and A.M.Gronenborn (1995).
The solution structure of the Mu Ner protein reveals a helix-turn-helix DNA recognition motif.
  Structure, 3, 1087-1095.
PDB codes: 1neq 1ner
  7651403 Y.Zhang, and B.J.Rollins (1995).
A dominant negative inhibitor indicates that monocyte chemoattractant protein 1 functions as a dimer.
  Mol Cell Biol, 15, 4851-4855.  
  7703852 D.G.Covell, G.W.Smythers, A.M.Gronenborn, and G.M.Clore (1994).
Analysis of hydrophobicity in the alpha and beta chemokine families and its relevance to dimerization.
  Protein Sci, 3, 2064-2072.  
  7849597 F.F.Damberger, J.G.Pelton, C.J.Harrison, H.C.Nelson, and D.E.Wemmer (1994).
Solution structure of the DNA-binding domain of the heat shock transcription factor determined by multidimensional heteronuclear magnetic resonance spectroscopy.
  Protein Sci, 3, 1806-1821.
PDB code: 2hsf
  7922028 J.Qin, G.M.Clore, and A.M.Gronenborn (1994).
The high-resolution three-dimensional solution structures of the oxidized and reduced states of human thioredoxin.
  Structure, 2, 503-522.
PDB codes: 1trs 1tru 1trv 1trw
  7881904 R.T.Clubb, J.G.Omichinski, H.Savilahti, K.Mizuuchi, A.M.Gronenborn, and G.M.Clore (1994).
A novel class of winged helix-turn-helix protein: the DNA-binding domain of Mu transposase.
  Structure, 2, 1041-1048.
PDB codes: 1tns 1tnt
7710711 T.J.Schall, and K.B.Bacon (1994).
Chemokines, leukocyte trafficking, and inflammation.
  Curr Opin Immunol, 6, 865-873.  
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.