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PDBsum entry 2q7n

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protein ligands Protein-protein interface(s) links
Cytokine receptor/cytokine PDB id
2q7n
Jmol
Contents
Protein chains
480 a.a. *
180 a.a. *
Ligands
NAG-FUC-NAG ×5
NAG-NAG ×7
NAG ×3
NAG-NAG-MAN-MAN
NAG-FUC-NAG-MAN
NAG-FUC-NAG-MAN-
MAN
* Residue conservation analysis
PDB id:
2q7n
Name: Cytokine receptor/cytokine
Title: Crystal structure of leukemia inhibitory factor in complex w receptor (domains 1-5)
Structure: Leukemia inhibitory factor receptor. Chain: a, c. Synonym: lif receptor, lif-r, d-factor/lif receptor, cd118 engineered: yes. Leukemia inhibitory factor. Chain: b, d. Synonym: lif, differentiation-stimulating factor, d factor, derived lpl inhibitor, mlpli, emfilermin. Engineered: yes
Source: Mus musculus. House mouse. Organism_taxid: 10090. Gene: lifr. Expressed in: cricetulus griseus. Expression_system_taxid: 10029. Homo sapiens. Human. Organism_taxid: 9606.
Resolution:
4.00Å     R-factor:   0.240     R-free:   0.287
Authors: T.Huyton,J.G.Zhang,N.A.Nicola,T.P.J.Garrett
Key ref:
T.Huyton et al. (2007). An unusual cytokine:Ig-domain interaction revealed in the crystal structure of leukemia inhibitory factor (LIF) in complex with the LIF receptor. Proc Natl Acad Sci U S A, 104, 12737-12742. PubMed id: 17652170 DOI: 10.1073/pnas.0705577104
Date:
07-Jun-07     Release date:   31-Jul-07    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P42703  (LIFR_MOUSE) -  Leukemia inhibitory factor receptor
Seq:
Struc:
 
Seq:
Struc:
 
Seq:
Struc:
1092 a.a.
480 a.a.
Protein chains
Pfam   ArchSchema ?
P15018  (LIF_HUMAN) -  Leukemia inhibitory factor
Seq:
Struc:
202 a.a.
180 a.a.
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular region   3 terms 
  Biological process     positive regulation of mesenchymal to epithelial transition involved in metanephros morphogenesis   38 terms 
  Biochemical function     RNA polymerase II transcription factor recruiting transcription factor activity     5 terms  

 

 
DOI no: 10.1073/pnas.0705577104 Proc Natl Acad Sci U S A 104:12737-12742 (2007)
PubMed id: 17652170  
 
 
An unusual cytokine:Ig-domain interaction revealed in the crystal structure of leukemia inhibitory factor (LIF) in complex with the LIF receptor.
T.Huyton, J.G.Zhang, C.S.Luo, M.Z.Lou, D.J.Hilton, N.A.Nicola, T.P.Garrett.
 
  ABSTRACT  
 
Leukemia inhibitory factor (LIF) receptor is a cell surface receptor that mediates the actions of LIF and other IL-6 type cytokines through the formation of high-affinity signaling complexes with gp130. Here we present the crystal structure of a complex of mouse LIF receptor with human LIF at 4.0 A resolution. The structure is, to date, the largest cytokine receptor fragment determined by x-ray crystallography. The binding of LIF to its receptor via the central Ig-like domain is unlike other cytokine receptor complexes that bind ligand predominantly through their cytokine-binding modules. This structure, in combination with previous crystallographic studies, also provides a structural template to understand the formation and orientation of the high-affinity signaling complex between LIF, LIF receptor, and gp130.
 
  Selected figure(s)  
 
Figure 1.
The crystal structure of the hLIF: mLIFR complex. (A) Side view of the complex illustrating the molecular surface for one complex, with receptor colored raspberry and ligand colored orange-gray. The NCS copy of the artificial dimer is shown in ribbons with receptor colored blue; ligand colored light blue; disulfide bonds colored orange, and N-linked carbohydrate colored yellow. (B) A detailed view of the receptor alone with domains and sites of posttranslational modifications labeled. Colors are as in A. (C) A domain representation of selected cytokine receptors illustrating differences in their modular domain structure.
Figure 2.
A stereo view of the hLIF:mLIFR binding interface. The receptor Ig-D4 domain secondary structure is shown as light blue ribbons. Interface residues are shown as sticks and colored yellow for receptor, salmon for ligand, and magenta for residues Pro-51, Lys-153, Phe-156 and Lys-159, previously demonstrated as essential residues for ligand binding (12).
 
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21315447 N.Nishishita, H.Ijiri, C.Takenaka, K.Kobayashi, K.Goto, E.Kotani, T.Itoh, H.Mori, and S.Kawamata (2011).
The use of leukemia inhibitory factor immobilized on virus-derived polyhedra to support the proliferation of mouse embryonic and induced pluripotent stem cells.
  Biomaterials, 32, 3555-3563.  
19920145 S.Le Saux, F.Rousseau, F.Barbier, E.Ravon, L.Grimaud, Y.Danger, J.Froger, S.Chevalier, and H.Gascan (2010).
Molecular dissection of human interleukin-31-mediated signal transduction through site-directed mutagenesis.
  J Biol Chem, 285, 3470-3477.  
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.  
18775332 G.Skiniotis, P.J.Lupardus, M.Martick, T.Walz, and K.C.Garcia (2008).
Structural organization of a full-length gp130/LIF-R cytokine receptor transmembrane complex.
  Mol Cell, 31, 737-748.
PDB code: 3e0g
18680750 P.J.Lupardus, and K.C.Garcia (2008).
The structure of interleukin-23 reveals the molecular basis of p40 subunit sharing with interleukin-12.
  J Mol Biol, 382, 931-941.
PDB code: 3duh
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.