PDBsum entry 1egj

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Immune system PDB id
Protein chains
101 a.a. *
215 a.a. *
220 a.a. *
Waters ×144
* Residue conservation analysis
PDB id:
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)
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
15-Feb-00     Release date:   15-Feb-01    
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Protein chain
Pfam   ArchSchema ?
P32927  (IL3RB_HUMAN) -  Cytokine receptor common subunit beta
897 a.a.
101 a.a.
Protein chain
Pfam   ArchSchema ?
P01661  (KV3A9_MOUSE) -  Ig kappa chain V-III region MOPC 63
131 a.a.
215 a.a.*
Protein chain
Pfam   ArchSchema ?
P01865  (GCAM_MOUSE) -  Ig gamma-2A chain C region, membrane-bound form
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.
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.  
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