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Cytokine PDB id
2h24
Jmol
Contents
Protein chain
139 a.a. *
Waters ×85
* Residue conservation analysis
PDB id:
2h24
Name: Cytokine
Title: Crystal structure of human il-10
Structure: Interleukin-10. Chain: a. Synonym: il-10, cytokine synthesis inhibitory factor, csif. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562
Biol. unit: Dimer (from PDB file)
Resolution:
2.00Å     R-factor:   0.204     R-free:   0.254
Authors: S.I.Yoon,M.R.Walter
Key ref:
S.I.Yoon et al. (2006). Conformational changes mediate interleukin-10 receptor 2 (IL-10R2) binding to IL-10 and assembly of the signaling complex. J Biol Chem, 281, 35088-35096. PubMed id: 16982608 DOI: 10.1074/jbc.M606791200
Date:
18-May-06     Release date:   17-Oct-06    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P22301  (IL10_HUMAN) -  Interleukin-10
Seq:
Struc: 		178 a.a.
139 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular region   3 terms 
  Biological process     negative regulation of growth of symbiont in host   51 terms 
  Biochemical function     cytokine activity     3 terms  

 

 
DOI no: 10.1074/jbc.M606791200 J Biol Chem 281:35088-35096 (2006)
PubMed id: 16982608  
 
 
Conformational changes mediate interleukin-10 receptor 2 (IL-10R2) binding to IL-10 and assembly of the signaling complex.
S.I.Yoon, N.J.Logsdon, F.Sheikh, R.P.Donnelly, M.R.Walter.
 
  ABSTRACT  
 
Interleukin-10 receptor 2 (IL-10R2) is a critical component of the IL-10.IL-10R1.IL-10R2 complex which regulates IL-10-mediated immunomodulatory responses. The ternary IL-10 signaling complex is assembled in a sequential order with the IL-10.IL-10R1 interaction occurring first followed by engagement of the IL-10R2 chain. In this study we map the IL-10R2 binding site on IL-10 using surface plasmon resonance and cell-based assays. Critical IL-10R2 binding residues are located in helix A adjacent to the previously identified IL-10R1 recognition surface. Interestingly, IL-10R2 binding residues located in the N-terminal end of helix A exhibit large structural differences between unbound cIL-10 and cIL-10.IL-10R1 crystal structures. This suggests IL-10R1-induced conformational changes regulate IL-10R2 binding and assembly of the ternary IL-10.IL-10R1.IL-10R2 complex. The basic mechanistic features of the assembly process are likely shared by six additional class-2 cytokines (viral IL-10s, IL-22, IL-26, IL-28A, IL28B, and IL-29) to promote IL-10R2 binding to six additional receptor complexes. These studies highlight the importance of structure in regulating low affinity protein-protein interactions and IL-10 signal transduction.
 
  Selected figure(s)  
 
Figure 3.
FIGURE 3. Characterization of cIL-10 dimer IL-10R2 binding site mutants. A, dissociation constants (K[d]) determined by SPR for cIL-10 mutant-sIL-10R1 interactions are plotted as black bars. Schematic diagram depicting the kinetic SPR experiment used to obtain the values is shown to the right of the figure. B, relative IL-10R2 binding by cIL-10 mutants. IL-10R2 binding to cIL-10 or cIL-10 mutant-sIL-10R1 complexes were evaluated in a single point assay normalized to the wild-type cIL-10·IL-10R2 response. A schematic diagram depicting the SPR experimental setup used to obtain the data is shown to the right of the figure. The results for both assays are expressed as the mean of multiple experiments ± S.D. Statistically significant differences (p < 0.05) between cIL-10 and cIL-10 mutants in the assays are denoted by asterisks (^*). C, Western blot showing the ability of cIL-10 dimer mutants to induce phosphorylation of STAT3 in primary human monocytes. pY, phosphotyrosine. 		Figure 5.
FIGURE 5. Comparison of sIL-10R2 binding sites. A, helices A and D from cIL-10 (magenta) and cmvIL-10 (blue) are shown. cIL-10 side-chain residues around the IL-10R2 binding site are gold. Structurally similar side-chain residues for cmvIL-10 are white. B, helices A and D from cIL-10 (magenta) and IL-22 (green) are shown. cIL-10 side-chain residues around the IL-10R2 binding site are gold as described for A. Side chains that contribute to the IL-22·IL-10R2 binding interface are shown in cyan. The labels of the most energetically important residues are circled.
 
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2006, 281, 35088-35096) copyright 2006.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21166540 W.Ouyang, S.Rutz, N.K.Crellin, P.A.Valdez, and S.G.Hymowitz (2011).
Regulation and functions of the IL-10 family of cytokines in inflammation and disease.
  Annu Rev Immunol, 29, 71.  
20846897 A.Zdanov (2010).
Structural analysis of cytokines comprising the IL-10 family.
  Cytokine Growth Factor Rev, 21, 325-330.  
20615107 B.Dénes, I.Fodor, and W.H.Langridge (2010).
Autoantigens plus interleukin-10 suppress diabetes autoimmunity.
  Diabetes Technol Ther, 12, 649-661.  
20454917 D.B.Trivella, J.R.Ferreira-Júnior, L.Dumoutier, J.C.Renauld, and I.Polikarpov (2010).
Structure and function of interleukin-22 and other members of the interleukin-10 family.
  Cell Mol Life Sci, 67, 2909-2935.  
20655797 K.Witte, E.Witte, R.Sabat, and K.Wolk (2010).
IL-28A, IL-28B, and IL-29: promising cytokines with type I interferon-like properties.
  Cytokine Growth Factor Rev, 21, 237-251.  
20947410 R.P.Donnelly, F.Sheikh, H.Dickensheets, R.Savan, H.A.Young, and M.R.Walter (2010).
Interleukin-26: an IL-10-related cytokine produced by Th17 cells.
  Cytokine Growth Factor Rev, 21, 393-401.  
21115385 R.Sabat, G.Grütz, K.Warszawska, S.Kirsch, E.Witte, K.Wolk, and J.Geginat (2010).
Biology of interleukin-10.
  Cytokine Growth Factor Rev, 21, 331-344.  
20462497 S.I.Yoon, B.C.Jones, N.J.Logsdon, B.D.Harris, A.Deshpande, S.Radaeva, B.A.Halloran, B.Gao, and M.R.Walter (2010).
Structure and mechanism of receptor sharing by the IL-10R2 common chain.
  Structure, 18, 638-648.
PDB code: 3lqm
19141282 C.A.McElroy, J.A.Dohm, and S.T.Walsh (2009).
Structural and biophysical studies of the human IL-7/IL-7Ralpha complex.
  Structure, 17, 54-65.
PDB codes: 3di2 3di3
19457860 H.H.Gad, C.Dellgren, O.J.Hamming, S.Vends, S.R.Paludan, and R.Hartmann (2009).
Interferon-lambda is functionally an interferon but structurally related to the interleukin-10 family.
  J Biol Chem, 284, 20869-20875.
PDB code: 3hhc
18599299 B.C.Jones, N.J.Logsdon, and M.R.Walter (2008).
Structure of IL-22 bound to its high-affinity IL-22R1 chain.
  Structure, 16, 1333-1344.
PDB code: 3dgc
17910059 J.J.Ellis, and S.Jones (2008).
Evaluating conformational changes in protein structures binding RNA.
  Proteins, 70, 1518-1526.  
18024507 M.de Oliveira Neto, J.R.Ferreira, D.Colau, H.Fischer, A.S.Nascimento, A.F.Craievich, L.Dumoutier, J.C.Renauld, and I.Polikarpov (2008).
Interleukin-22 forms dimers that are recognized by two interleukin-22R1 receptor chains.
  Biophys J, 94, 1754-1765.  
19016528 S.G.Gruber, M.Gloria Luciani, P.Grundtner, A.Zdanov, and C.Gasche (2008).
Differential signaling of cmvIL-10 through common variants of the IL-10 receptor 1.
  Eur J Immunol, 38, 3365-3375.  
18074396 R.L.Rich, and D.G.Myszka (2007).
Survey of the year 2006 commercial optical biosensor literature.
  J Mol Recognit, 20, 300-366.  
17224278 S.I.Yoon, and M.R.Walter (2007).
Identification and characterization of a +1 frameshift observed during the expression of Epstein-Barr virus IL-10 in Escherichia coli.
  Protein Expr Purif, 53, 132-137.  
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.