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Cytokine PDB id
1alu
Jmol
Contents
Protein chain
157 a.a. *
Ligands
SO4 ×4
TLA
Waters ×120
* Residue conservation analysis
PDB id:
1alu
Name: Cytokine
Title: Human interleukin-6
Structure: Interleukin-6. Chain: a. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562
Biol. unit: Dimer (from PQS)
Resolution:
1.90Å     R-factor:   0.213     R-free:   0.277
Authors: W.S.Somers,M.Stahl,J.S.Seehra
Key ref:
W.Somers et al. (1997). 1.9 A crystal structure of interleukin 6: implications for a novel mode of receptor dimerization and signaling. EMBO J, 16, 989-997. PubMed id: 9118960 DOI: 10.1093/emboj/16.5.989
Date:
03-Jun-97     Release date:   03-Jun-98    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P05231  (IL6_HUMAN) -  Interleukin-6
Seq:
Struc: 		212 a.a.
157 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular region   1 term 
  Biological process     immune response   1 term 
  Biochemical function     cytokine activity     2 terms  

 

 
DOI no: 10.1093/emboj/16.5.989 EMBO J 16:989-997 (1997)
PubMed id: 9118960  
 
 
1.9 A crystal structure of interleukin 6: implications for a novel mode of receptor dimerization and signaling.
W.Somers, M.Stahl, J.S.Seehra.
 
  ABSTRACT  
 
Interleukin 6 (IL-6) has many biological activities in vivo, and deregulation has been implicated in many disease processes. IL-6, a 185 amino acid polypeptide was refolded, purified and crystallized. The crystals diffracted to beyond 1.9 A and the structure was solved using single isomorphous replacement. The X-ray structure of IL-6 is composed of a four helix bundle linked by loops and an additional mini-helix. 157 out of 185 residues are well defined in the final structure, with 18 N-terminal and 8 A-B loop amino acids displaying no interpretable electron density. The three-dimensional structure has been used to construct a model of IL-6 interacting with the IL-6 receptor (alpha-chain) and gp130 (beta-chain) that gives new insight into the process of molecular recognition and signaling. Based on this model, we predict a fourth binding site on IL-6, a low affinity IL-6-IL-6 interaction, which may be necessary for the sequential assembly of a functional hexameric IL-6 receptor complex.
 
  Selected figure(s)  
 
Figure 2.
Figure 2 Stereo view of the water structure in the region between the D helix and the A -B loop of IL-6. The water molecules are shown as red spheres and the protein as a stick representation. 		Figure 4.
Figure 4 (A) A ribbon representation of the IL-6, IL-6r and gp130 hexamer signaling model. The IL-6 crystal structure is shown in green, IL-6r in blue and gp130 in red. The proposed binding sites are labeled. Site 1 is the site of IL-6 -IL-6r interactions. Site 2 is the region where IL-6 interacts with gp130 in the trimer. Site 3 is the site of IL-6 -gp130 interactions between trimers. Site 4 is the location of IL-6 -IL-6 interactions between trimers. (B) A ribbon representation of IL-6 with space-filling atoms of exposed side chains found to alter IL-6r binding (site 1) or gp130 binding (sites 2 or 3) when mutated.
 
  The above figures are reprinted from an Open Access publication published by Macmillan Publishers Ltd: EMBO J (1997, 16, 989-997) copyright 1997.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
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Mesoporous carbide-derived carbon with porosity tuned for efficient adsorption of cytokines.
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Hexameric structure and assembly of the interleukin-6/IL-6 alpha-receptor/gp130 complex.
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11238858 H.Li, H.Wang, and J.Nicholas (2001).
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16232993 H.Mizuguchi, H.Mizuno, K.Yasukawa, T.Ishiguro, K.Fukui, T.Imanaka, and M.Takagi (2001).
Enhanced signal transduction by a directly fused protein of interleukin-6 and its receptor.
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Signaling through a novel domain of gp130 mediates cell proliferation and activation of Hck and Erk kinases.
  Mol Cell Biol, 21, 8068-8081.  
11405230 P.Igaz, S.Bösze, S.Tóth, A.Falus, and F.Hudecz (2001).
C-terminal peptides of interleukin-6 modulate the expression of junB protooncogene and the production of fibrinogen by HepG2 cells.
  Biol Chem, 382, 669-676.  
11558598 T.Harada, E.Kurimoto, Y.Moriyama, D.Ejima, T.Sakai, D.Nohara, and K.Kato (2001).
Application of combined reagent solution to the oxidative refolding of recombinant human interleukin 6.
  Chem Pharm Bull (Tokyo), 49, 1128-1131.  
10835339 J.Bravo, and J.K.Heath (2000).
Receptor recognition by gp130 cytokines.
  EMBO J, 19, 2399-2411.  
10684643 J.M.Matthews, R.S.Norton, A.Hammacher, and R.J.Simpson (2000).
The single mutation Phe173 --> Ala induces a molten globule-like state in murine interleukin-6.
  Biochemistry, 39, 1942-1950.  
  10997905 M.C.Deller, K.R.Hudson, S.Ikemizu, J.Bravo, E.Y.Jones, and J.K.Heath (2000).
Crystal structure and functional dissection of the cytostatic cytokine oncostatin M.
  Structure, 8, 863-874.
PDB code: 1evs
10848977 S.H.Hoischen, P.Vollmer, P.März, S.Ozbek, K.S.Götze, C.Peschel, T.Jostock, T.Geib, J.Müllberg, S.Mechtersheimer, M.Fischer, J.Grötzinger, P.R.Galle, and S.Rose-John (2000).
Human herpes virus 8 interleukin-6 homologue triggers gp130 on neuronal and hematopoietic cells.
  Eur J Biochem, 267, 3604-3612.  
10813527 Y.Aoki, K.D.Jones, and G.Tosato (2000).
Kaposi's sarcoma-associated herpesvirus-encoded interleukin-6.
  J Hematother Stem Cell Res, 9, 137-145.  
18726347 Y.Ren, J.Feng, H.Qu, S.Li, and B.Shen (2000).
Three-dimensional structure and function study on the active region in the extracellular ligand-binding domain of human IL-6 receptor.
  Sci China C Life Sci, 43, 425-432.  
10066782 A.R.Cole, N.E.Hall, H.R.Treutlein, J.S.Eddes, G.E.Reid, R.L.Moritz, and R.J.Simpson (1999).
Disulfide bond structure and N-glycosylation sites of the extracellular domain of the human interleukin-6 receptor.
  J Biol Chem, 274, 7207-7215.  
10095017 H.Hampel, S.J.Teipel, F.Padberg, A.Haslinger, M.Riemenschneider, M.J.Schwarz, H.U.Kötter, M.Scheloske, K.Buch, S.Stübner, R.Dukoff, R.Lasser, N.Müller, T.Sunderland, S.I.Rapoport, and H.J.Möller (1999).
Discriminant power of combined cerebrospinal fluid tau protein and of the soluble interleukin-6 receptor complex in the diagnosis of Alzheimer's disease.
  Brain Res, 823, 104-112.  
10504396 I.Tacken, H.Dahmen, O.Boisteau, S.Minvielle, Y.Jacques, J.Grötzinger, A.Küster, U.Horsten, C.Blanc, F.A.Montero-Julian, P.C.Heinrich, and G.Müller-Newen (1999).
Definition of receptor binding sites on human interleukin-11 by molecular modeling-guided mutagenesis.
  Eur J Biochem, 265, 645-655.  
  10364379 J.A.Kaleeba, E.P.Bergquam, and S.W.Wong (1999).
A rhesus macaque rhadinovirus related to Kaposi's sarcoma-associated herpesvirus/human herpesvirus 8 encodes a functional homologue of interleukin-6.
  J Virol, 73, 6177-6181.  
10494829 J.Grötzinger, T.Kernebeck, K.J.Kallen, and S.Rose-John (1999).
IL-6 type cytokine receptor complexes: hexamer, tetramer or both?
  Biol Chem, 380, 803-813.  
10207005 K.J.Kallen, J.Grötzinger, E.Lelièvre, P.Vollmer, D.Aasland, C.Renné, J.Müllberg, K.H.Myer zum Büschenfelde, H.Gascan, and S.Rose-John (1999).
Receptor recognition sites of cytokines are organized as exchangeable modules. Transfer of the leukemia inhibitory factor receptor-binding site from ciliary neurotrophic factor to interleukin-6.
  J Biol Chem, 274, 11859-11867.  
  10342555 R.A.Gadient, and P.H.Patterson (1999).
Leukemia inhibitory factor, Interleukin 6, and other cytokines using the GP130 transducing receptor: roles in inflammation and injury.
  Stem Cells, 17, 127-137.  
9880494 T.Rakemann, M.Niehof, S.Kubicka, M.Fischer, M.P.Manns, S.Rose-John, and C.Trautwein (1999).
The designer cytokine hyper-interleukin-6 is a potent activator of STAT3-dependent gene transcription in vivo and in vitro.
  J Biol Chem, 274, 1257-1266.  
10026196 V.A.Barton, K.R.Hudson, and J.K.Heath (1999).
Identification of three distinct receptor binding sites of murine interleukin-11.
  J Biol Chem, 274, 5755-5761.  
9501088 J.Bravo, D.Staunton, J.K.Heath, and E.Y.Jones (1998).
Crystal structure of a cytokine-binding region of gp130.
  EMBO J, 17, 1665-1674.
PDB code: 1bqu
9692957 J.M.Matthews, A.Hammacher, G.J.Howlett, and R.J.Simpson (1998).
Physicochemical characterization of an antagonistic human interleukin-6 dimer.
  Biochemistry, 37, 10671-10680.  
9593715 M.G.Hinds, T.Maurer, J.G.Zhang, N.A.Nicola, and R.S.Norton (1998).
Solution structure of leukemia inhibitory factor.
  J Biol Chem, 273, 13738-13745.
PDB code: 1a7m
9419340 R.J.Duhé, G.A.Evans, R.A.Erwin, R.A.Kirken, G.W.Cox, and W.L.Farrar (1998).
Nitric oxide and thiol redox regulation of Janus kinase activity.
  Proc Natl Acad Sci U S A, 95, 126-131.  
9694899 S.Ozbek, J.Grötzinger, B.Krebs, M.Fischer, A.Wollmer, T.Jostock, J.Müllberg, and S.Rose-John (1998).
The membrane proximal cytokine receptor domain of the human interleukin-6 receptor is sufficient for ligand binding but not for gp130 association.
  J Biol Chem, 273, 21374-21379.  
9342320 M.Karpusas, M.Nolte, C.B.Benton, W.Meier, W.N.Lipscomb, and S.Goelz (1997).
The crystal structure of human interferon beta at 2.2-A resolution.
  Proc Natl Acad Sci U S A, 94, 11813-11818.
PDB code: 1au1
  9144766 R.J.Simpson, A.Hammacher, D.K.Smith, J.M.Matthews, and L.D.Ward (1997).
Interleukin-6: structure-function relationships.
  Protein Sci, 6, 929-955.  
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.