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PDBsum entry 1ilm

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protein Protein-protein interface(s) links
Cytokine PDB id
1ilm
Jmol PyMol
Contents
Protein chains
128 a.a.
61 a.a.
200 a.a.
192 a.a.
Theoretical model
PDB id:
1ilm
Name: Cytokine
Structure: Interleukin-2 complex (model a) (theoretical model)
Source: Human (homo sapiens)
Authors: P.Bamborough,C.J.Hedgecock,W.G.Richards
Key ref:
P.Bamborough et al. (1994). The interleukin-2 and interleukin-4 receptors studied by molecular modelling. Structure, 2, 839-851. PubMed id: 7529123 DOI: 10.1016/S0969-2126(94)00085-9
Date:
09-Sep-94     Release date:   26-Jan-95    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
No UniProt id for this chain
Protein chain
Pfam   ArchSchema ?
P01589  (IL2RA_HUMAN) -  Interleukin-2 receptor subunit alpha
Seq:
Struc:
272 a.a.
61 a.a.
Protein chain
Pfam   ArchSchema ?
P14784  (IL2RB_HUMAN) -  Interleukin-2 receptor subunit beta
Seq:
Struc:
 
Seq:
Struc:
551 a.a.
200 a.a.
Protein chain
Pfam   ArchSchema ?
P31785  (IL2RG_HUMAN) -  Cytokine receptor common subunit gamma
Seq:
Struc:
369 a.a.
192 a.a.
Key:    PfamA domain  PfamB domain  Secondary structure

 

 
DOI no: 10.1016/S0969-2126(94)00085-9 Structure 2:839-851 (1994)
PubMed id: 7529123  
 
 
The interleukin-2 and interleukin-4 receptors studied by molecular modelling.
P.Bamborough, C.J.Hedgecock, W.G.Richards.
 
  ABSTRACT  
 
BACKGROUND: Interleukin-2 (IL2) and interleukin-4 (IL4) are members of the four-helix bundle family of cytokines, whose receptors show similarity to each other and to the growth hormone receptor fold. These proteins help to control, among other things, the rate of clonal expansion of lymphocytes, and thus play an important role in the regulation of the immune system. They are therefore of interest as transmembrane signalling proteins, as well as potential pharmaceutical targets. RESULTS: We have modelled structures of the extracellular components of the IL2 and IL4 receptors based on the structure of the complex of human growth hormone with its receptor, and incorporating the recently discovered shared gamma c chain. The models provide possible explanations for several experimental observations, including those from site-directed mutagenesis around the binding sites. Receptor residues that may be close to important side chains on IL2 and IL4 are identified and possible effects of their mutation are discussed. A comparison is made between the models and the growth hormone complex, and between the gamma c chain bound to IL2 and to IL4. CONCLUSIONS: The models offer structural explanations for observed behaviour such as the effects of mutation of the A- and D-helices of the cytokines. In addition, they may be of use in the identification of residues which may interact in the ligand-receptor interfaces, and which would therefore be worthy of further investigation.
 
  Selected figure(s)  
 
Figure 6.
Figure 6. A topology diagram of the SCR fold. Arrows denote extended structure, and locations of disulphide bonds are indicated by heavy dashed lines. Faint dashed lines connect regions of extended structure linked by hydrogen bonds. The variable region is marked ‘V’. Figure 6. A topology diagram of the SCR fold. Arrows denote extended structure, and locations of disulphide bonds are indicated by heavy dashed lines. Faint dashed lines connect regions of extended structure linked by hydrogen bonds. The variable region is marked ‘V’.
Figure 7.
Figure 7. Alignment between the sequences of complement factor H domains 5, 15 and 16 [58], and human IL2α domains 1 and 2 [39]. Regions of extended structure in the complement domains are boxed; residues forming the core of the SCR domains that are broadly conserved as hydrophobic are shown as white type on black. Conserved cysteines are connected by solid lines, the position of a potential disulphide bond in IL2α domain 1 is indicated by a dashed line. Figure 7. Alignment between the sequences of complement factor H domains 5, 15 and 16 [[3]58], and human IL2α domains 1 and 2 [[4]39]. Regions of extended structure in the complement domains are boxed; residues forming the core of the SCR domains that are broadly conserved as hydrophobic are shown as white type on black. Conserved cysteines are connected by solid lines, the position of a potential disulphide bond in IL2α domain 1 is indicated by a dashed line.
 
  The above figures are reprinted by permission from Cell Press: Structure (1994, 2, 839-851) copyright 1994.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
16586495 A.E.Frankel, A.Surendranathan, J.H.Black, A.White, K.Ganjoo, and L.D.Cripe (2006).
Phase II clinical studies of denileukin diftitox diphtheria toxin fusion protein in patients with previously treated chronic lymphocytic leukemia.
  Cancer, 106, 2158-2164.  
17001647 A.Quéméner, J.Bernard, E.Mortier, A.Plet, Y.Jacques, and V.Tran (2006).
Docking of human interleukin-15 to its specific receptor alpha chain: correlation between molecular modeling and mutagenesis experimental data.
  Proteins, 65, 623-636.  
15933202 M.Rickert, X.Wang, M.J.Boulanger, N.Goriatcheva, and K.C.Garcia (2005).
The structure of interleukin-2 complexed with its alpha receptor.
  Science, 308, 1477-1480.
PDB code: 1z92
15039446 J.Bernard, C.Harb, E.Mortier, A.Quéméner, R.H.Meloen, C.Vermot-Desroches, J.Wijdeness, P.van Dijken, J.Grötzinger, J.W.Slootstra, A.Plet, and Y.Jacques (2004).
Identification of an interleukin-15alpha receptor-binding site on human interleukin-15.
  J Biol Chem, 279, 24313-24322.  
  12718740 A.E.Frankel, D.R.Fleming, B.L.Powell, and R.Gartenhaus (2003).
DAB389IL2 (ONTAK) fusion protein therapy of chronic lymphocytic leukaemia.
  Expert Opin Biol Ther, 3, 179-186.  
12676936 T.Rose, J.L.Moreau, R.Eckenberg, and J.Thèze (2003).
Structural analysis and modeling of a synthetic interleukin-2 mimetic and its interleukin-2Rbeta2 receptor.
  J Biol Chem, 278, 22868-22876.  
11815609 F.Olosz, and T.R.Malek (2002).
Structural basis for binding multiple ligands by the common cytokine receptor gamma-chain.
  J Biol Chem, 277, 12047-12052.  
11874464 J.L.Zhang, M.Buehner, and W.Sebald (2002).
Functional epitope of common gamma chain for interleukin-4 binding.
  Eur J Biochem, 269, 1490-1499.  
10662798 R.Eckenberg, T.Rose, J.L.Moreau, R.Weil, F.Gesbert, S.Dubois, D.Tello, M.Bossus, H.Gras, A.Tartar, J.Bertoglio, S.Chouaïb, M.Goldberg, Y.Jacques, P.M.Alzari, and J.Thèze (2000).
The first alpha helix of interleukin (IL)-2 folds as a homotetramer, acts as an agonist of the IL-2 receptor beta chain, and induces lymphokine-activated killer cells.
  J Exp Med, 191, 529-540.  
10223295 M.H.Seto, H.L.Liu, D.A.Zajchowski, and M.Whitlow (1999).
Protein fold analysis of the B30.2-like domain.
  Proteins, 35, 235-249.  
10501244 P.Rajananthanan, G.S.Attard, N.A.Sheikh, and W.J.Morrow (1999).
Novel aggregate structure adjuvants modulate lymphocyte proliferation and Th1 and Th2 cytokine profiles in ovalbumin immunized mice.
  Vaccine, 18, 140-152.  
10219247 T.Hage, W.Sebald, and P.Reinemer (1999).
Crystal structure of the interleukin-4/receptor alpha chain complex reveals a mosaic binding interface.
  Cell, 97, 271-281.
PDB code: 1iar
9789059 A.Whitty, N.Raskin, D.L.Olson, C.W.Borysenko, C.M.Ambrose, C.D.Benjamin, and L.C.Burkly (1998).
Interaction affinity between cytokine receptor components on the cell surface.
  Proc Natl Acad Sci U S A, 95, 13165-13170.  
9022007 D.J.Matthews, L.Hibbert, K.Friedrich, A.Minty, and R.E.Callard (1997).
X-SCID B cell responses to interleukin-4 and interleukin-13 are mediated by a receptor complex that includes the interleukin-4 receptor alpha chain (p140) but not the gamma c chain.
  Eur J Immunol, 27, 116-121.  
9399950 N.Sharfe, M.Shahar, and C.M.Roifman (1997).
An interleukin-2 receptor gamma chain mutation with normal thymus morphology.
  J Clin Invest, 100, 3036-3043.  
9050834 Y.Wang, B.J.Shen, and W.Sebald (1997).
A mixed-charge pair in human interleukin 4 dominates high-affinity interaction with the receptor alpha chain.
  Proc Natl Acad Sci U S A, 94, 1657-1662.  
  8797861 B.J.Shen, T.Hage, and W.Sebald (1996).
Global and local determinants for the kinetics of interleukin-4/interleukin-4 receptor alpha chain interaction. A biosensor study employing recombinant interleukin-4-binding protein.
  Eur J Biochem, 240, 252-261.  
7705343 A.Duschl (1995).
An antagonistic mutant of interleukin-4 fails to recruit gamma c into the receptor complex. Characterization by specific crosslinking.
  Eur J Biochem, 228, 305-310.  
8529628 A.Lischke, W.Kammer, and K.Friedrich (1995).
Different human interleukin-4 mutants preferentially activate human or murine common receptor gamma chain.
  Eur J Biochem, 234, 100-107.  
  7613464 M.H.Seto, R.N.Harkins, M.Adler, M.Whitlow, W.B.Church, and E.Croze (1995).
Homology model of human interferon-alpha 8 and its receptor complex.
  Protein Sci, 4, 655-670.  
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.

 

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