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PDBsum entry 1b2t

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protein links
Chemokine PDB id
1b2t
Jmol
Contents
Protein chain
77 a.a. *
* Residue conservation analysis
PDB id:
1b2t
Name: Chemokine
Title: Solution structure of the cx3c chemokine domain of fractalkine
Structure: Protein (fractalkine). Chain: a. Fragment: chemokine domain. Engineered: yes. Other_details: disulfide between 8 and 34 and 12 and 50
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562. Expression_system_variant: plyss.
NMR struc: 20 models
Authors: T.M.Handel,L.S.Mizoue,J.F.Bazan,E.C.Johnson
Key ref:
L.S.Mizoue et al. (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. PubMed id: 9931005 DOI: 10.1021/bi9820614
Date:
01-Dec-98     Release date:   08-Apr-99    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P78423  (X3CL1_HUMAN) -  Fractalkine
Seq:
Struc:
397 a.a.
77 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   2 terms 
  Biological process     immune response   1 term 
  Biochemical function     chemokine activity     1 term  

 

 
DOI no: 10.1021/bi9820614 Biochemistry 38:1402-1414 (1999)
PubMed id: 9931005  
 
 
Solution structure and dynamics of the CX3C chemokine domain of fractalkine and its interaction with an N-terminal fragment of CX3CR1.
L.S.Mizoue, J.F.Bazan, E.C.Johnson, T.M.Handel.
 
  ABSTRACT  
 
Fractalkine, a novel CX3C chemokine, is unusual because of both its membrane-associated structure and its direct role in cell adhesion. We have solved the solution structure of the chemokine domain of fractalkine (residues 1-76) by heteronuclear NMR methods. The 20 lowest energy structures in the ensemble have an average backbone rmsd of 0.43 A, excluding the termini. In contrast to many other chemokines which form homodimers, fractalkine's chemokine module is monomeric. Comparison of the structure to CC and CXC chemokines reveals interesting differences which are likely to be relevant to receptor binding. These include a bulge formed by the CX3C motif, the relative orientation of the N-terminus and 30's loop (residues 30-38), and the conformation of the N-loop (residues 9-19). 15N backbone relaxation experiments indicate that these same regions of the protein are dynamic. We also titrated 15N-labeled protein with a peptide from the N-terminus of the receptor CX3CR1 and confirmed that this region of the receptor contacts the fractalkine chemokine domain. Interestingly, the binding site maps roughly to the regions of greatest flexibility and structural variability. Together, these data provide a first glimpse of how fractalkine interacts with its receptor and should help guide mutagenesis studies to further elucidate the molecular details of binding and signaling through CX3CR1.
 

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.  
21492740 H.Liu, and D.Jiang (2011).
Fractalkine/CX3CR1 and atherosclerosis.
  Clin Chim Acta, 412, 1180-1186.  
20117133 J.L.Galzi, M.Hachet-Haas, D.Bonnet, F.Daubeuf, S.Lecat, M.Hibert, J.Haiech, and N.Frossard (2010).
Neutralizing endogenous chemokines with small molecules. Principles and potential therapeutic applications.
  Pharmacol Ther, 126, 39-55.  
19681642 A.Ravindran, P.R.Joseph, and K.Rajarathnam (2009).
Structural basis for differential binding of the interleukin-8 monomer and dimer to the CXCR1 N-domain: role of coupled interactions and dynamics.
  Biochemistry, 48, 8795-8805.  
18930713 M.Chen, M.Cai, D.McPherson, V.Hruby, C.M.Harmon, and Y.Yang (2009).
Contribution of the transmembrane domain 6 of melanocortin-4 receptor to peptide [Pro5, DNal (2')8]-gamma-MSH selectivity.
  Biochem Pharmacol, 77, 114-124.  
19743876 Y.Yang, V.J.Hruby, M.Chen, C.Crasto, M.Cai, and C.M.Harmon (2009).
Novel binding motif of ACTH analogues at the melanocortin receptors.
  Biochemistry, 48, 9775-9784.  
18799424 C.T.Veldkamp, C.Seibert, F.C.Peterson, N.B.De la Cruz, J.C.Haugner, H.Basnet, T.P.Sakmar, and B.F.Volkman (2008).
Structural basis of CXCR4 sulfotyrosine recognition by the chemokine SDF-1/CXCL12.
  Sci Signal, 1, ra4.
PDB codes: 2k01 2k03 2k04 2k05
  18218997 J.Liu, S.Louie, W.Hsu, K.M.Yu, H.B.Nicholas, and G.L.Rosenquist (2008).
Tyrosine sulfation is prevalent in human chemokine receptors important in lung disease.
  Am J Respir Cell Mol Biol, 38, 738-743.  
18725411 P.Hermand, F.Pincet, S.Carvalho, H.Ansanay, E.Trinquet, M.Daoudi, C.Combadière, and P.Deterre (2008).
Functional Adhesiveness of the CX3CL1 Chemokine Requires Its Aggregation: ROLE OF THE TRANSMEMBRANE DOMAIN.
  J Biol Chem, 283, 30225-30234.  
17304353 C.Cheng, D.Tempel, R.van Haperen, H.C.de Boer, D.Segers, M.Huisman, A.J.van Zonneveld, P.J.Leenen, A.van der Steen, P.W.Serruys, R.de Crom, and R.Krams (2007).
Shear stress-induced changes in atherosclerotic plaque composition are modulated by chemokines.
  J Clin Invest, 117, 616-626.  
17071104 C.T.Veldkamp, F.C.Peterson, P.L.Hayes, J.E.Mattmiller, J.C.Haugner, N.de la Cruz, and B.F.Volkman (2007).
On-column refolding of recombinant chemokines for NMR studies and biological assays.
  Protein Expr Purif, 52, 202-209.  
17222184 H.Fernando, G.T.Nagle, and K.Rajarathnam (2007).
Thermodynamic characterization of interleukin-8 monomer binding to CXCR1 receptor N-terminal domain.
  FEBS J, 274, 241-251.  
17545153 M.Chen, M.Cai, C.J.Aprahamian, K.E.Georgeson, V.Hruby, C.M.Harmon, and Y.Yang (2007).
Contribution of the conserved amino acids of the melanocortin-4 receptor in [corrected] [Nle4,D-Phe7]-alpha-melanocyte-stimulating [corrected] hormone binding and signaling.
  J Biol Chem, 282, 21712-21719.  
17437419 R.Colobran, R.Pujol-Borrell, M.P.Armengol, and M.Juan (2007).
The chemokine network. I. How the genomic organization of chemokines contains clues for deciphering their functional complexity.
  Clin Exp Immunol, 148, 208-217.  
17291188 S.J.Allen, S.E.Crown, and T.M.Handel (2007).
Chemokine: receptor structure, interactions, and antagonism.
  Annu Rev Immunol, 25, 787-820.  
17151939 Y.Becker (2007).
The spreading of HIV-1 infection in the human organism is caused by fractalkine trafficking of the infected lymphocytes--a review, hypothesis and implications for treatment.
  Virus Genes, 34, 93.  
16678487 C.Weber, and R.R.Koenen (2006).
Fine-tuning leukocyte responses: towards a chemokine 'interactome'.
  Trends Immunol, 27, 268-273.  
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.  
17075134 O.K.Baryshnikova, and B.D.Sykes (2006).
Backbone dynamics of SDF-1alpha determined by NMR: interpretation in the presence of monomer-dimer equilibrium.
  Protein Sci, 15, 2568-2578.  
15880599 A.Inoue, H.Hasegawa, M.Kohno, M.R.Ito, M.Terada, T.Imai, O.Yoshie, M.Nose, and S.Fujita (2005).
Antagonist of fractalkine (CX3CL1) delays the initiation and ameliorates the progression of lupus nephritis in MRL/lpr mice.
  Arthritis Rheum, 52, 1522-1533.  
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.  
15039444 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.  
12486712 K.L.Mayer, and M.J.Stone (2003).
Backbone dynamics of the CC-chemokine eotaxin-2 and comparison among the eotaxin group chemokines.
  Proteins, 50, 184-191.  
11909868 A.M.Fong, S.M.Alam, T.Imai, B.Haribabu, and D.D.Patel (2002).
CX3CR1 tyrosine sulfation enhances fractalkine-induced cell adhesion.
  J Biol Chem, 277, 19418-19423.  
11839303 C.A.Andersen, A.G.Palmer, S.Brunak, and B.Rost (2002).
Continuum secondary structure captures protein flexibility.
  Structure, 10, 175-184.  
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.  
11867522 S.P.Curran, D.Leuenberger, W.Oppliger, and C.M.Koehler (2002).
The Tim9p-Tim10p complex binds to the transmembrane domains of the ADP/ATP carrier.
  EMBO J, 21, 942-953.  
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.  
  11583978 M.V.Volin, J.M.Woods, M.A.Amin, M.A.Connors, L.A.Harlow, and A.E.Koch (2001).
Fractalkine: a novel angiogenic chemokine in rheumatoid arthritis.
  Am J Pathol, 159, 1521-1530.  
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
10660527 A.M.Fong, H.P.Erickson, J.P.Zachariah, S.Poon, N.J.Schamberg, T.Imai, and D.D.Patel (2000).
Ultrastructure and function of the fractalkine mucin domain in CX(3)C chemokine domain presentation.
  J Biol Chem, 275, 3781-3786.  
  11152129 Buyong, J.Xiong, J.Lubkowski, and R.Nussinov (2000).
Homology modeling and molecular dynamics simulations of lymphotactin.
  Protein Sci, 9, 2192-2199.  
11041848 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: 1cm9
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
10805752 S.Jung, J.Aliberti, P.Graemmel, M.J.Sunshine, G.W.Kreutzberg, A.Sher, and D.R.Littman (2000).
Analysis of fractalkine receptor CX(3)CR1 function by targeted deletion and green fluorescent protein reporter gene insertion.
  Mol Cell Biol, 20, 4106-4114.  
  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
10467150 E.C.Johnson, G.A.Lazar, J.R.Desjarlais, and T.M.Handel (1999).
Solution structure and dynamics of a designed hydrophobic core variant of ubiquitin.
  Structure, 7, 967-976.
PDB code: 1ud7
  10631975 G.A.Lazar, E.C.Johnson, J.R.Desjarlais, and T.M.Handel (1999).
Rotamer strain as a determinant of protein structural specificity.
  Protein Sci, 8, 2598-2610.
PDB code: 1c3t
10508776 H.N.Moseley, and G.T.Montelione (1999).
Automated analysis of NMR assignments and structures for proteins.
  Curr Opin Struct Biol, 9, 635-642.  
  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.  
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.