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PDBsum entry 1gh7
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protein ligands Protein-protein interface(s) links
Cytokine receptor PDB id
1gh7

 

 

 

 

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Contents
Protein chain
408 a.a. *
Ligands
NAG-NAG-BMA ×2
NAG-NAG-FUC ×2
* Residue conservation analysis
PDB id:
1gh7
Name: Cytokine receptor
Title: Crystal structure of the complete extracellular domain of the beta- common receptor of il-3, il-5, and gm-csf
Structure: Cytokine receptor common beta chain. Chain: a, b. Fragment: extracellular domain. Engineered: yes. Mutation: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Cell_line: cell line hl60 derived from a promyelocytic leukemia. Expressed in: trichoplusia ni. Expression_system_taxid: 7111. Expression_system_cell_line: bti-tn-5bi-4 (high five) invitrogen. Polyhedrosis virus (baculovirus).
Biol. unit: Dimer (from PQS)
Resolution:
3.00Å     R-factor:   0.267     R-free:   0.307
Authors: 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,I.G.Young
Key ref:
P.D.Carr et al. (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. PubMed id: 11207369 DOI: 10.1016/S0092-8674(01)00213-6
Date:
27-Nov-00     Release date:   28-Nov-01    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
P32927  (IL3RB_HUMAN) -  Cytokine receptor common subunit beta from Homo sapiens
Seq:
Struc: 		 
Seq:
Struc: 		897 a.a.
408 a.a.*
Key:    Secondary structure  CATH domain
* PDB and UniProt seqs differ at 2 residue positions (black crosses)

 

 
DOI no: 10.1016/S0092-8674(01)00213-6 Cell 104:291-300 (2001)
PubMed id: 11207369  
 
 
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.
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, I.G.Young.
 
  ABSTRACT  
 
The receptor systems for the hemopoietic cytokines GM-CSF, IL-3, and IL-5 consist of ligand-specific alpha receptor subunits that play an essential role in the activation of the shared betac subunit, the major signaling entity. Here, we report the structure of the complete betac extracellular domain. It has a structure unlike any class I cytokine receptor described thus far, forming a stable interlocking dimer in the absence of ligand in which the G strand of domain 1 hydrogen bonds into the corresponding beta sheet of domain 3 of the dimer-related molecule. The G strand of domain 3 similarly partners with the dimer-related domain 1. The structure provides new insights into receptor activation by the respective alpha receptor:ligand complexes.
 
  Selected figure(s)  
 
Figure 3.
Figure 3. Structure of Domain 4The positions of the side chains that form the Trp–Arg zipper and those of the “affinity converting” residues are shown. 		Figure 6.
Figure 6. Surface Plots Produced by GRASP ([19])Orientations of the molecule are the same as in Figure 1. Color coding: green, hydrophobic regions; and blue, polar regions.
 
  The above figures are reprinted by permission from Cell Press: Cell (2001, 104, 291-300) copyright 2001.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20802515 B.Uberti, P.Dentelli, A.Rosso, P.Defilippi, and M.F.Brizzi (2010).
Inhibition of β1 integrin and IL-3Rβ common subunit interaction hinders tumour angiogenesis.
  Oncogene, 29, 6581-6590.  
20554759 J.Suthaus, A.Tillmann, I.Lorenzen, E.Bulanova, S.Rose-John, and J.Scheller (2010).
Forced homo- and heterodimerization of all gp130-type receptor complexes leads to constitutive ligand-independent signaling and cytokine-independent growth.
  Mol Biol Cell, 21, 2797-2807.  
19634988 M.A.Wouters, S.W.Fan, and N.L.Haworth (2010).
Disulfides as redox switches: from molecular mechanisms to functional significance.
  Antioxid Redox Signal, 12, 53-91.  
20078425 S.Mirza, A.Walker, J.Chen, J.M.Murphy, and I.G.Young (2010).
The Ig-like domain of human GM-CSF receptor alpha plays a critical role in cytokine binding and receptor activation.
  Biochem J, 426, 307-317.  
19109256 J.Chen, J.Olsen, S.Ford, S.Mirza, A.Walker, J.M.Murphy, and I.G.Young (2009).
A New Isoform of Interleukin-3 Receptor {alpha} with Novel Differentiation Activity and High Affinity Binding Mode.
  J Biol Chem, 284, 5763-5773.  
19223217 M.Perugini, A.Varelias, T.Sadlon, and R.J.D'Andrea (2009).
Hematopoietic growth factor mimetics: from concept to clinic.
  Cytokine Growth Factor Rev, 20, 87-94.  
19352505 R.Dey, K.Ji, Z.Liu, and L.Chen (2009).
A cytokine-cytokine interaction in the assembly of higher-order structure and activation of the interleukine-3:receptor complex.
  PLoS ONE, 4, e5188.  
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.  
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.  
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
  18678938 G.Hansen, T.R.Hercus, Y.Xu, A.F.Lopez, M.W.Parker, and W.J.McKinstry (2008).
Crystallization and preliminary X-ray diffraction analysis of the ternary human GM-CSF receptor complex.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 64, 711-714.  
18326494 M.Zaks-Zilberman, A.E.Harrington, T.Ishino, and I.M.Chaiken (2008).
Interleukin-5 receptor subunit oligomerization and rearrangement revealed by fluorescence resonance energy transfer imaging.
  J Biol Chem, 283, 13398-13406.  
18294864 T.Ishino, A.E.Harrington, M.Zaks-Zilberman, J.J.Scibek, and I.Chaiken (2008).
Slow-dissociation effect of common signaling subunit beta c on IL5 and GM-CSF receptor assembly.
  Cytokine, 42, 179-190.  
17960150 M.E.Call, and K.W.Wucherpfennig (2007).
Common themes in the assembly and architecture of activating immune receptors.
  Nat Rev Immunol, 7, 841-850.  
17215754 X.Z.Ran, Y.P.Su, Z.W.Zong, C.H.Guo, H.E.Zheng, X.H.Chen, G.P.Ai, and T.M.Cheng (2007).
Effects of serum from rats with combined radiation-burn injury on the growth of hematopoietic progenitor cells.
  J Trauma, 62, 193-198.  
16624864 C.Stuhlmann-Laeisz, S.Lang, A.Chalaris, P.Krzysztof, S.Enge, J.Eichler, U.Klingmüller, M.Samuel, M.Ernst, S.Rose-John, and J.Scheller (2006).
Forced dimerization of gp130 leads to constitutive STAT3 activation, cytokine-independent growth, and blockade of differentiation of embryonic stem cells.
  Mol Biol Cell, 17, 2986-2995.  
  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
15840566 L.Zabeau, D.Defeau, H.Iserentant, J.Vandekerckhove, F.Peelman, and J.Tavernier (2005).
Leptin receptor activation depends on critical cysteine residues in its fibronectin type III subdomains.
  J Biol Chem, 280, 22632-22640.  
15771567 M.E.Call, and K.W.Wucherpfennig (2005).
The T cell receptor: critical role of the membrane environment in receptor assembly and function.
  Annu Rev Immunol, 23, 101-125.  
15060062 J.M.Murphy, S.C.Ford, J.E.Olsen, S.E.Gustin, P.D.Jeffrey, D.L.Ollis, and I.G.Young (2004).
Interleukin-3 binding to the murine betaIL-3 and human betac receptors involves functional epitopes formed by domains 1 and 4 of different protein chains.
  J Biol Chem, 279, 26500-26508.  
15152191 M.E.Call, J.Pyrdol, and K.W.Wucherpfennig (2004).
Stoichiometry of the T-cell receptor-CD3 complex and key intermediates assembled in the endoplasmic reticulum.
  EMBO J, 23, 2348-2357.  
12853652 I.Lemmens, S.Eyckerman, L.Zabeau, D.Catteeuw, E.Vertenten, K.Verschueren, D.Huylebroeck, J.Vandekerckhove, and J.Tavernier (2003).
Heteromeric MAPPIT: a novel strategy to study modification-dependent protein-protein interactions in mammalian cells.
  Nucleic Acids Res, 31, e75.  
12832402 J.Braunstein, S.Brutsaert, R.Olson, and C.Schindler (2003).
STATs dimerize in the absence of phosphorylation.
  J Biol Chem, 278, 34133-34140.  
12525483 J.M.Murphy, S.C.Ford, U.M.Wiedemann, P.D.Carr, D.L.Ollis, and I.G.Young (2003).
A novel functional epitope formed by domains 1 and 4 of the human common beta-subunit is involved in receptor activation by granulocyte macrophage colony-stimulating factor and interleukin 5.
  J Biol Chem, 278, 10572-10577.  
14500898 S.Wong, J.McLaughlin, D.Cheng, K.Shannon, L.Robb, and O.N.Witte (2003).
IL-3 receptor signaling is dispensable for BCR-ABL-induced myeloproliferative disease.
  Proc Natl Acad Sci U S A, 100, 11630-11635.  
14653823 T.C.Cheung, and J.P.Hearn (2003).
Development of a baculovirus-based fluorescence resonance energy transfer assay for measuring protein-protein interaction.
  Eur J Biochem, 270, 4973-4981.  
12461182 J.N.Varghese, R.L.Moritz, M.Z.Lou, A.Van Donkelaar, H.Ji, N.Ivancic, K.M.Branson, N.E.Hall, and R.J.Simpson (2002).
Structure of the extracellular domains of the human interleukin-6 receptor alpha -chain.
  Proc Natl Acad Sci U S A, 99, 15959-15964.
PDB codes: 1n26 1n2q
11834739 M.B.Voisin, J.Bitard, S.Daburon, J.F.Moreau, and J.L.Taupin (2002).
Separate functions for the two modules of the membrane-proximal cytokine binding domain of glycoprotein 190, the leukemia inhibitory factor low affinity receptor, in ligand binding and receptor activation.
  J Biol Chem, 277, 13682-13692.  
11976492 M.Roth, P.Carpentier, O.Kaïkati, J.Joly, P.Charrault, M.Pirocchi, R.Kahn, E.Fanchon, L.Jacquamet, F.Borel, A.Bertoni, P.Israel-Gouy, and J.L.Ferrer (2002).
FIP: a highly automated beamline for multiwavelength anomalous diffraction experiments.
  Acta Crystallogr D Biol Crystallogr, 58, 805-814.  
  11606572 J.L.Taupin, P.Legembre, J.Bitard, S.Daburon, V.Pitard, F.Blanchard, L.Duplomb, A.Godard, Y.Jacques, and J.F.Moreau (2001).
Identification of agonistic and antagonistic antibodies against gp190, the leukemia inhibitory factor receptor, reveals distinct roles for its two cytokine-binding domains.
  J Biol Chem, 276, 47975-47981.  
  11748263 M.Martinez-Moczygemba, and D.P.Huston (2001).
Proteasomal regulation of betac signaling reveals a novel mechanism for cytokine receptor heterotypic desensitization.
  J Clin Invest, 108, 1797-1806.  
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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