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PDBsum entry 1egj

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protein ligands Protein-protein interface(s) links
Immune system PDB id
1egj
Jmol
Contents
Protein chains
101 a.a. *
215 a.a. *
220 a.a. *
Ligands
NAG
Waters ×144
* Residue conservation analysis
PDB id:
1egj
Name: Immune system
Title: Domain 4 of the beta common chain in complex with an antibod
Structure: Cytokine receptor common beta chain precursor. Chain: a. Fragment: domain 4. Engineered: yes. Antibody (light chain). Chain: l. Antibody (heavy chain). Chain: h
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562. Mus musculus. House mouse. Organism_taxid: 10090. Other_details: monoclonal antibody.
Biol. unit: Trimer (from PQS)
Resolution:
2.80Å     R-factor:   0.228     R-free:   0.288
Authors: J.Rossjohn,W.J.Mckinstry,J.M.Woodcock,B.J.Mcclure,T.R.Hercus M.W.Parker,A.F.Lopez,C.J.Bagley
Key ref: J.Rossjohn et al. (2000). Structure of the activation domain of the GM-CSF/IL-3/IL-5 receptor common beta-chain bound to an antagonist. Blood, 95, 2491-2498. PubMed id: 10753826
Date:
15-Feb-00     Release date:   15-Feb-01    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P32927  (IL3RB_HUMAN) -  Cytokine receptor common subunit beta
Seq:
Struc:
 
Seq:
Struc:
897 a.a.
101 a.a.
Protein chain
Pfam   ArchSchema ?
P01661  (KV3A9_MOUSE) -  Ig kappa chain V-III region MOPC 63
Seq:
Struc:
131 a.a.
215 a.a.*
Protein chain
Pfam   ArchSchema ?
P01865  (GCAM_MOUSE) -  Ig gamma-2A chain C region, membrane-bound form
Seq:
Struc:
398 a.a.
220 a.a.*
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 8 residue positions (black crosses)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     membrane   1 term 
  Biochemical function     antigen binding     2 terms  

 

 
Blood 95:2491-2498 (2000)
PubMed id: 10753826  
 
 
Structure of the activation domain of the GM-CSF/IL-3/IL-5 receptor common beta-chain bound to an antagonist.
J.Rossjohn, W.J.McKinstry, J.M.Woodcock, B.J.McClure, T.R.Hercus, M.W.Parker, A.F.Lopez, C.J.Bagley.
 
  ABSTRACT  
 
Heterodimeric cytokine receptors generally consist of a major cytokine-binding subunit and a signaling subunit. The latter can transduce signals by more than 1 cytokine, as exemplified by the granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-2 (IL-2), and IL-6 receptor systems. However, often the signaling subunits in isolation are unable to bind cytokines, a fact that has made it more difficult to obtain structural definition of their ligand-binding sites. This report details the crystal structure of the ligand-binding domain of the GM-CSF/IL-3/IL-5 receptor beta-chain (beta(c)) signaling subunit in complex with the Fab fragment of the antagonistic monoclonal antibody, BION-1. This is the first single antagonist of all 3 known eosinophil-producing cytokines, and it is therefore capable of regulating eosinophil-related diseases such as asthma. The structure reveals a fibronectin type III domain, and the antagonist-binding site involves major contributions from the loop between the B and C strands and overlaps the cytokine-binding site. Furthermore, tyrosine(421) (Tyr(421)), a key residue involved in receptor activation, lies in the neighboring loop between the F and G strands, although it is not immediately adjacent to the cytokine-binding residues in the B-C loop. Interestingly, functional experiments using receptors mutated across these loops demonstrate that they are cooperatively involved in full receptor activation. The experiments, however, reveal subtle differences between the B-C loop and Tyr(421), which is suggestive of distinct functional roles. The elucidation of the structure of the ligand-binding domain of beta(c) also suggests how different cytokines recognize a single receptor subunit, which may have implications for homologous receptor systems. (Blood. 2000;95:2491-2498)
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
19436055 T.R.Hercus, D.Thomas, M.A.Guthridge, P.G.Ekert, J.King-Scott, M.W.Parker, and A.F.Lopez (2009).
The granulocyte-macrophage colony-stimulating factor receptor: linking its structure to cell signaling and its role in disease.
  Blood, 114, 1289-1298.  
18692472 G.Hansen, T.R.Hercus, B.J.McClure, F.C.Stomski, M.Dottore, J.Powell, H.Ramshaw, J.M.Woodcock, Y.Xu, M.Guthridge, W.J.McKinstry, A.F.Lopez, and M.W.Parker (2008).
The structure of the GM-CSF receptor complex reveals a distinct mode of cytokine receptor activation.
  Cell, 134, 496-507.
PDB code: 3cxe
  16754968 P.D.Carr, F.Conlan, S.Ford, D.L.Ollis, and I.G.Young (2006).
An improved resolution structure of the human beta common receptor involved in IL-3, IL-5 and GM-CSF signalling which gives better definition of the high-affinity binding epitope.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 62, 509-513.
PDB code: 2gys
15456912 M.Brines, G.Grasso, F.Fiordaliso, A.Sfacteria, P.Ghezzi, M.Fratelli, R.Latini, Q.W.Xie, J.Smart, C.J.Su-Rick, E.Pobre, D.Diaz, D.Gomez, C.Hand, T.Coleman, and A.Cerami (2004).
Erythropoietin mediates tissue protection through an erythropoietin and common beta-subunit heteroreceptor.
  Proc Natl Acad Sci U S A, 101, 14907-14912.  
12960396 C.S.Clements, H.H.Reid, T.Beddoe, F.E.Tynan, M.A.Perugini, T.G.Johns, C.C.Bernard, and J.Rossjohn (2003).
The crystal structure of myelin oligodendrocyte glycoprotein, a key autoantigen in multiple sclerosis.
  Proc Natl Acad Sci U S A, 100, 11059-11064.
PDB code: 1py9
11264710 H.S.Ramshaw, J.M.Woodcock, C.J.Bagley, B.J.McClure, T.R.Hercus, and A.F.Lopez (2001).
New approaches in the treatment of asthma.
  Immunol Cell Biol, 79, 154-159.  
11207369 P.D.Carr, S.E.Gustin, A.P.Church, J.M.Murphy, S.C.Ford, D.A.Mann, D.M.Woltring, I.Walker, D.L.Ollis, and I.G.Young (2001).
Structure of the complete extracellular domain of the common beta subunit of the human GM-CSF, IL-3, and IL-5 receptors reveals a novel dimer configuration.
  Cell, 104, 291-300.
PDB code: 1gh7
11358507 S.E.Gustin, A.P.Church, S.C.Ford, D.A.Mann, P.D.Carr, D.L.Ollis, and I.G.Young (2001).
Expression, crystallization and derivatization of the complete extracellular domain of the beta(c) subunit of the human IL-5, IL-3 and GM-CSF receptors.
  Eur J Biochem, 268, 2905-2911.  
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.