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PDBsum entry 1n2q

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protein ligands Protein-protein interface(s) links
Cytokine PDB id
1n2q
Jmol
Contents
Protein chains
301 a.a.
299 a.a.
166 a.a.
Ligands
CYS ×2
Theoretical model
PDB id:
1n2q
Name: Cytokine
Title: A model of the extra-cellular hexameric signalling complex of il-6/il-6 receptor and gp130
Structure: Interleukin-6 receptor beta chain. Chain: a, b. Fragment: first 3 extracellular domains. Synonym: gp130. Interleukin-6 receptor alpha chain. Chain: c, d. Fragment: residues 1-325. Synonym: il-6r-alpha. Interleukin-6.
Source: Homo sapiens. Human. Human
Authors: J.N.Varghese,R.L.Moritz,M.-Z.Lou,A.Van Donkelaar,H.Ji, N.Ivancic,K.M.Branson,N.E.Hall,R.J.Simpson
Key ref:
J.N.Varghese et al. (2002). Structure of the extracellular domains of the human interleukin-6 receptor alpha -chain. Proc Natl Acad Sci U S A, 99, 15959-15964. PubMed id: 12461182 DOI: 10.1073/pnas.232432399
Date:
24-Oct-02     Release date:   18-Dec-02    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P40189  (IL6RB_HUMAN) -  Interleukin-6 receptor subunit beta
Seq:
Struc:
 
Seq:
Struc:
918 a.a.
301 a.a.
Protein chains
Pfam   ArchSchema ?
P08887  (IL6RA_HUMAN) -  Interleukin-6 receptor subunit alpha
Seq:
Struc:
468 a.a.
299 a.a.
Protein chains
Pfam   ArchSchema ?
P05231  (IL6_HUMAN) -  Interleukin-6
Seq:
Struc:
212 a.a.
166 a.a.
Key:    PfamA domain  Secondary structure

 

 
DOI no: 10.1073/pnas.232432399 Proc Natl Acad Sci U S A 99:15959-15964 (2002)
PubMed id: 12461182  
 
 
Structure of the extracellular domains of the human interleukin-6 receptor alpha -chain.
J.N.Varghese, R.L.Moritz, M.Z.Lou, A.Van Donkelaar, H.Ji, N.Ivancic, K.M.Branson, N.E.Hall, R.J.Simpson.
 
  ABSTRACT  
 
Dysregulated production of IL-6 and its receptor (IL-6R) are implicated in the pathogenesis of multiple myeloma, autoimmune diseases and prostate cancer. The IL-6R complex comprises two molecules each of IL-6, IL-6R, and the signaling molecule, gp130. Here, we report the x-ray structure (2.4 A) of the IL-6R ectodomains. The N-terminal strand of the Ig-like domain (D(1)) is disulfide-bonded to domain D(2), and domains D(2) and D(3), the cytokine-binding domain, are structurally similar to known cytokine-binding domains. The head-to-tail packing of two closely associated IL-6R molecules observed in the crystal may be representative of the configuration of the physiological dimer of IL-6R and provides new insight into the architecture of the IL-6R complex.
 
  Selected figure(s)  
 
Figure 4.
Fig 4. The dimer interface of IL-6R showing the region of interaction by red, green, blue, purple, and cyan areas representing interdimeric distances (58) of less than 5, 4, 3, 2, and 1 Å, respectively. The view is rotated 180° relative to the view in Fig. 1; the crystal twofold axis is vertical, and the membrane is horizontal below the molecule.
Figure 6.
Fig 6. (a) Space-filling model of the proposed hexameric receptor complex, consisting of two molecules each of IL-6, IL-6R, and gp130 chains (shown in purple and blue, light and dark green, orange and red, respectively). IL-6 is labeled with the binding sites I, II, and III. (b) A modular representation of the hexameric complex (D[1]-D[6] are labeled 1-6) colored as in a, but with the additional three fibronectin domains (D[4]-D[6]) of gp130 that have not been modeled placed to indicate how the association of the two D[5'] modules from both gp130 molecules, under the "tunnel" of the IL-6R dimer, can activate signaling by dimerization of the cytoplasmic domains (white circles). The membrane proximal extracellular region of IL-6R (49 residues) is shown as an extended chain connecting IL-6R to the membrane.
 
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20157276 R.E.Gillilan, M.J.Cook, S.W.Cornaby, and D.H.Bilderback (2010).
Microcrystallography using single-bounce monocapillary optics.
  J Synchrotron Radiat, 17, 227-236.  
19635415 M.Y.Wiesinger, S.Haan, S.Wüller, M.E.Kauffmann, T.Recker, A.Küster, P.C.Heinrich, and G.Müller-Newen (2009).
Development of an IL-6 inhibitor based on the functional analysis of murine IL-6Ralpha(1).
  Chem Biol, 16, 783-794.  
18817510 X.Wang, P.Lupardus, S.L.Laporte, and K.C.Garcia (2009).
Structural biology of shared cytokine receptors.
  Annu Rev Immunol, 27, 29-60.  
18941632 M.Cardó-Vila, A.J.Zurita, R.J.Giordano, J.Sun, R.Rangel, L.Guzman-Rojas, C.D.Anobom, A.P.Valente, F.C.Almeida, J.Lahdenranta, M.G.Kolonin, W.Arap, and R.Pasqualini (2008).
A ligand peptide motif selected from a cancer patient is a receptor-interacting site within human interleukin-11.
  PLoS ONE, 3, e3452.  
18407769 Y.Ohsugi, and T.Kishimoto (2008).
The recombinant humanized anti-IL-6 receptor antibody tocilizumab, an innovative drug for the treatment of rheumatoid arthritis.
  Expert Opin Biol Ther, 8, 669-681.  
17986189 J.J.Velarde, K.M.Varney, K.G.Inman, M.Farfan, E.Dudley, J.Fletcher, D.J.Weber, and J.P.Nataro (2007).
Solution structure of the novel dispersin protein of enteroaggregative Escherichia coli.
  Mol Microbiol, 66, 1123-1135.
PDB code: 2jvu
17437716 R.Matadeen, W.C.Hon, J.K.Heath, E.Y.Jones, and S.Fuller (2007).
The dynamics of signal triggering in a gp130-receptor complex.
  Structure, 15, 441-448.  
17652170 T.Huyton, J.G.Zhang, C.S.Luo, M.Z.Lou, D.J.Hilton, N.A.Nicola, and T.P.Garrett (2007).
An unusual cytokine:Ig-domain interaction revealed in the crystal structure of leukemia inhibitory factor (LIF) in complex with the LIF receptor.
  Proc Natl Acad Sci U S A, 104, 12737-12742.
PDB code: 2q7n
17978466 Y.Ohsugi (2007).
Recent advances in immunopathophysiology of interleukin-6: an innovative therapeutic drug, tocilizumab (recombinant humanized anti-human interleukin-6 receptor antibody), unveils the mysterious etiology of immune-mediated inflammatory diseases.
  Biol Pharm Bull, 30, 2001-2006.  
16972794 O.Hecht, A.J.Dingley, A.Schwanter, S.Ozbek, S.Rose-John, and J.Grötzinger (2006).
The solution structure of the membrane-proximal cytokine receptor domain of the human interleukin-6 receptor.
  Biol Chem, 387, 1255-1259.
PDB code: 2arw
16083340 B.E.Barton (2005).
Interleukin-6 and new strategies for the treatment of cancer, hyperproliferative diseases and paraneoplastic syndromes.
  Expert Opin Ther Targets, 9, 737-752.  
15861391 D.Perret, F.Rousseau, V.Tran, and H.Gascan (2005).
Reversal of some viral IL-6 electrostatic properties compared to IL-6 contributes to a loss of alpha receptor component recruitment.
  Proteins, 60, 14-26.  
15895091 G.Skiniotis, M.J.Boulanger, K.C.Garcia, and T.Walz (2005).
Signaling conformations of the tall cytokine receptor gp130 when in complex with IL-6 and IL-6 receptor.
  Nat Struct Mol Biol, 12, 545-551.  
15802951 N.K.Krishna (2005).
Identification of structural domains involved in astrovirus capsid biology.
  Viral Immunol, 18, 17-26.  
16462093 Y.Ohsugi, and N.Tsuchimoto (2005).
[Pharmacological and clinical profile of anti-human IL-6 receptor antibody (tocilizumab, ACTEMRA), a novel therapeutic drug for Castleman's disease]
  Nippon Yakurigaku Zasshi, 126, 419-425.  
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.