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Complex (cytokine receptor/antagonist) PDB id
1ira
Jmol
Contents
Protein chains
145 a.a. *
311 a.a. *
Ligands
NAG ×4
Waters ×86
* Residue conservation analysis
PDB id:
1ira
Name: Complex (cytokine receptor/antagonist)
Title: Complex of the interleukin-1 receptor with the interleukin-1 antagonist (il1ra)
Structure: Interleukin-1 receptor antagonist. Chain: x. Synonym: il1ra. Engineered: yes. Interleukin-1 receptor. Chain: y. Fragment: type i receptor, extracellular domains. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Cell_line: sf9. Expressed in: escherichia coli. Expression_system_taxid: 562. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Expression_system_cell_line: sf9.
Biol. unit: Dimer (from PQS)
Resolution:
2.70Å     R-factor:   0.213     R-free:   0.314
Authors: H.A.Schreuder,C.Tardif,S.Tramp-Kalmeyer,A.Soffientini,E.Saru A.Akeson,T.Bowlin,S.Yanofsky,R.W.Barrett
Key ref: H.Schreuder et al. (1997). A new cytokine-receptor binding mode revealed by the crystal structure of the IL-1 receptor with an antagonist. Nature, 386, 194-200. PubMed id: 9062194 DOI: 10.1038/386194a0
Date:
09-Apr-98     Release date:   17-Jun-98    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P18510  (IL1RA_HUMAN) -  Interleukin-1 receptor antagonist protein
Seq:
Struc: 		177 a.a.
145 a.a.
Protein chain
Pfam   ArchSchema ?
P14778  (IL1R1_HUMAN) -  Interleukin-1 receptor type 1
Seq:
Struc: 		 
Seq:
Struc: 		569 a.a.
311 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular region   7 terms 
  Biological process     immune response   4 terms 
  Biochemical function     protein binding     5 terms  

 

 
DOI no: 10.1038/386194a0 Nature 386:194-200 (1997)
PubMed id: 9062194  
 
 
A new cytokine-receptor binding mode revealed by the crystal structure of the IL-1 receptor with an antagonist.
H.Schreuder, C.Tardif, S.Trump-Kallmeyer, A.Soffientini, E.Sarubbi, A.Akeson, T.Bowlin, S.Yanofsky, R.W.Barrett.
 
  ABSTRACT  
 
Inflammation, regardless of whether it is provoked by infection or by tissue damage, starts with the activation of macrophages which initiate a cascade of inflammatory responses by producing the cytokines interleukin-1 (IL-1) and tumour necrosis factor-alpha (ref. 1). Three naturally occurring ligands for the IL-1 receptor (IL1R) exist: the agonists IL-1alpha and IL-1beta and the IL-1-receptor antagonist IL1RA (ref. 2). IL-1 is the only cytokine for which a naturally occurring antagonist is known. Here we describe the crystal structure at 2.7 A resolution of the soluble extracellular part of type-I IL1R complexed with IL1RA. The receptor consists of three immunoglobulin-like domains. Domains 1 and 2 are tightly linked, but domain three is completely separate and connected by a flexible linker. Residues of all three domains contact the antagonist and include the five critical IL1RA residues which were identified by site-directed mutagenesis. A region that is important for biological function in IL-1beta, the 'receptor trigger site' is not in direct contact with the receptor in the IL1RA complex. Modelling studies suggest that this IL-1beta trigger site might induce a movement of domain 3.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21228814 C.L.Gallant-Behm, P.Du, S.M.Lin, P.T.Marucha, L.A.DiPietro, and T.A.Mustoe (2011).
Epithelial regulation of mesenchymal tissue behavior.
  J Invest Dermatol, 131, 892-899.  
21481778 E.Karaca, and A.M.Bonvin (2011).
A multidomain flexible docking approach to deal with large conformational changes in the modeling of biomolecular complexes.
  Structure, 19, 555-565.  
20802483 D.Wang, S.Zhang, L.Li, X.Liu, K.Mei, and X.Wang (2010).
Structural insights into the assembly and activation of IL-1β with its receptors.
  Nat Immunol, 11, 905-911.
PDB code: 3o4o
20671916 J.H.Lee, L.C.Wang, H.H.Yu, Y.T.Lin, Y.H.Yang, and B.L.Chiang (2010).
Type I IL-1 receptor (IL-1RI) as potential new therapeutic target for bronchial asthma.
  Mediators Inflamm, 2010, 567351.  
19836339 A.Lingel, T.M.Weiss, M.Niebuhr, B.Pan, B.A.Appleton, C.Wiesmann, J.F.Bazan, and W.J.Fairbrother (2009).
Structure of IL-33 and its interaction with the ST2 and IL-1RAcP receptors--insight into heterotrimeric IL-1 signaling complexes.
  Structure, 17, 1398-1410.
PDB code: 2kll
19115392 A.W.Schmid, M.A.Lynch, and C.E.Herron (2009).
The effects of IL-1 receptor antagonist on beta amyloid mediated depression of LTP in the rat CA1 in vivo.
  Hippocampus, 19, 670-676.  
18569390 E.Dahlén, K.Barchan, D.Herrlander, P.Höjman, M.Karlsson, L.Ljung, M.Andersson, E.Bäckman, A.C.Hager, B.Walse, L.Joosten, and W.van den Berg (2008).
Development of interleukin-1 receptor antagonist mutants with enhanced antagonistic activity in vitro and improved therapeutic efficacy in collagen-induced arthritis.
  J Immunotoxicol, 5, 189-199.  
18650393 S.Gosavi, P.C.Whitford, P.A.Jennings, and J.N.Onuchic (2008).
Extracting function from a beta-trefoil folding motif.
  Proc Natl Acad Sci U S A, 105, 10384-10389.  
17340198 G.Vergoten, and J.P.Zanetta (2007).
Structural differences between the putative carbohydrate-recognition domains of human IL-1 alpha, IL-1 beta and IL-1 receptor antagonist obtained by in silico modeling.
  Glycoconj J, 24, 183-193.  
  19662225 J.M.Kneller, T.Ehlen, J.P.Matisic, D.Miller, D.Van Niekerk, W.L.Lam, M.Marra, R.Richards-Kortum, M.Follen, C.Macaulay, and S.J.Jones (2007).
Using LongSAGE to Detect Biomarkers of Cervical Cancer Potentially Amenable to Optical Contrast Agent Labelling.
  Biomark Insights, 2, 447-461.  
18003919 S.Ali, M.Huber, C.Kollewe, S.C.Bischoff, W.Falk, and M.U.Martin (2007).
IL-1 receptor accessory protein is essential for IL-33-induced activation of T lymphocytes and mast cells.
  Proc Natl Acad Sci U S A, 104, 18660-18665.  
15986350 R.L.Smeets, L.A.Joosten, O.J.Arntz, M.B.Bennink, N.Takahashi, H.Carlsen, M.U.Martin, W.B.van den Berg, and F.A.van de Loo (2005).
Soluble interleukin-1 receptor accessory protein ameliorates collagen-induced arthritis by a different mode of action from that of interleukin-1 receptor antagonist.
  Arthritis Rheum, 52, 2202-2211.  
  14746812 J.A.Langer, E.C.Cutrone, and S.Kotenko (2004).
The Class II cytokine receptor (CRF2) family: overview and patterns of receptor-ligand interactions.
  Cytokine Growth Factor Rev, 15, 33-48.  
14528293 Z.Kato, J.Jee, H.Shikano, M.Mishima, I.Ohki, H.Ohnishi, A.Li, K.Hashimoto, E.Matsukuma, K.Omoya, Y.Yamamoto, T.Yoneda, T.Hara, N.Kondo, and M.Shirakawa (2003).
The structure and binding mode of interleukin-18.
  Nat Struct Biol, 10, 966-971.
PDB code: 1j0s
12356774 D.E.Smith, R.R.Ketchem, H.Moore, Z.Anderson, B.R.Renshaw, D.J.Friend, and J.E.Sims (2002).
A single amino acid difference between human and monkey interleukin (IL)-1beta dictates effective binding to soluble type II IL-1 receptor.
  J Biol Chem, 277, 47619-47625.  
11790541 J.E.Sims (2002).
IL-1 and IL-18 receptors, and their extended family.
  Curr Opin Immunol, 14, 117-122.  
11972061 P.Aloy, and R.B.Russell (2002).
Interrogating protein interaction networks through structural biology.
  Proc Natl Acad Sci U S A, 99, 5896-5901.  
11790772 S.H.Kim, T.Azam, D.Novick, D.Y.Yoon, L.L.Reznikov, P.Bufler, M.Rubinstein, and C.A.Dinarello (2002).
Identification of amino acid residues critical for biological activity in human interleukin-18.
  J Biol Chem, 277, 10998-11003.  
  11772463 W.J.Kao, Y.Liu, R.Gundloori, J.Li, D.Lee, N.Einerson, J.Burmania, and K.Stevens (2002).
Engineering endogenous inflammatory cells as delivery vehicles.
  J Control Release, 78, 219-233.  
11312116 B.Spörri, M.Bickel, D.Dobbelaere, J.Machado, and D.Lottaz (2001).
Soluble interleukin-1 receptor--reverse signaling in innate immunoregulation.
  Cytokine Growth Factor Rev, 12, 27-32.  
  11574261 E.Dunn, J.E.Sims, M.J.Nicklin, and L.A.O'Neill (2001).
Annotating genes with potential roles in the immune system: six new members of the IL-1 family.
  Trends Immunol, 22, 533-536.  
11352744 V.M.Abramov, A.M.Vasiliev, R.N.Vasilenko, N.L.Kulikova, I.V.Kosarev, V.S.Khlebnikov, A.T.Ishchenko, S.MacIntyre, J.R.Gillespie, R.Khurana, T.Korpela, A.L.Fink, and V.N.Uversky (2001).
Structural and functional similarity between Yersinia pestis capsular protein Caf1 and human interleukin-1 beta.
  Biochemistry, 40, 6076-6084.  
11260252 Y.Tokura, M.Röcken, R.A.Clark, E.Haliasos, M.Takigawa, and A.A.Sinha (2001).
What are the most promising strategies for the therapeutic immunomodulation of allergic diseases?
  Exp Dermatol, 10, 128.  
  10736564 B.B.Loo, K.K.Darwish, S.S.Vainikka, J.J.Saarikettu, P.P.Vihko, J.J.Hermonen, A.A.Goldman, K.K.Alitalo, and M.M.Jalkanen (2000).
Production and characterization of the extracellular domain of recombinant human fibroblast growth factor receptor 4.
  Int J Biochem Cell Biol, 32, 489-497.  
10618369 D.J.Stauber, A.D.DiGabriele, and W.A.Hendrickson (2000).
Structural interactions of fibroblast growth factor receptor with its ligands.
  Proc Natl Acad Sci U S A, 97, 49-54.
PDB code: 1djs
  10986460 D.J.Thiel, M.H.le Du, R.L.Walter, A.D'Arcy, C.Chène, M.Fountoulakis, G.Garotta, F.K.Winkler, and S.E.Ealick (2000).
Observation of an unexpected third receptor molecule in the crystal structure of human interferon-gamma receptor complex.
  Structure, 8, 927-936.
PDB code: 1fg9
10880432 L.Mosyak, Y.Zhang, E.Glasfeld, S.Haney, M.Stahl, J.Seehra, and W.S.Somers (2000).
The bacterial cell-division protein ZipA and its interaction with an FtsZ fragment revealed by X-ray crystallography.
  EMBO J, 19, 3179-3191.
PDB codes: 1f46 1f47
10753817 M.C.Deller, and E.Yvonne Jones (2000).
Cell surface receptors.
  Curr Opin Struct Biol, 10, 213-219.  
10744718 S.Kumar, P.C.McDonnell, R.Lehr, L.Tierney, M.N.Tzimas, D.E.Griswold, E.A.Capper, R.Tal-Singer, G.I.Wells, M.L.Doyle, and P.R.Young (2000).
Identification and initial characterization of four novel members of the interleukin-1 family.
  J Biol Chem, 275, 10308-10314.  
10097093 G.Venkataraman, R.Raman, V.Sasisekharan, and R.Sasisekharan (1999).
Molecular characteristics of fibroblast growth factor-fibroblast growth factor receptor-heparin-like glycosaminoglycan complex.
  Proc Natl Acad Sci U S A, 96, 3658-3663.  
  10404599 M.T.Huhtala, O.T.Pentikäinen, and M.S.Johnson (1999).
A dimeric ternary complex of FGFR [correction of FGFR1], heparin and FGF-1 leads to an 'electrostatic sandwich' model for heparin binding.
  Structure, 7, 699-709.
PDB code: 1qct
9737881 L.A.Goldman, E.C.Cutrone, A.Dang, X.Hao, J.K.Lim, and J.A.Langer (1998).
Mapping human interferon-alpha (IFN-alpha 2) binding determinants of the type I interferon receptor subunit IFNAR-1 with human/bovine IFNAR-1 chimeras.
  Biochemistry, 37, 13003-13010.  
  9918122 P.E.Auron (1998).
The interleukin 1 receptor: ligand interactions and signal transduction.
  Cytokine Growth Factor Rev, 9, 221-237.  
9765311 P.Franco, O.Massa, M.Garcia-Rocha, F.Chiaradonna, C.Iaccarino, I.Correas, E.Mendez, J.Avila, F.Blasi, and M.P.Stoppelli (1998).
Protein kinase C-dependent in vivo phosphorylation of prourokinase leads to the formation of a receptor competitive antagonist.
  J Biol Chem, 273, 27734-27740.  
9597123 W.P.Arend, M.Malyak, C.J.Guthridge, and C.Gabay (1998).
Interleukin-1 receptor antagonist: role in biology.
  Annu Rev Immunol, 16, 27-55.  
9266165 B.C.Cunningham, and J.A.Wells (1997).
Minimized proteins.
  Curr Opin Struct Biol, 7, 457-462.  
9620641 C.A.Dinarello (1997).
Interleukin-1.
  Cytokine Growth Factor Rev, 8, 253-265.  
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.