Difference between revisions of "Part:BBa K554004"
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==Three-dimensional structure representation==
 
==Three-dimensional structure representation==
 +
You can find below a tridimensional structure of ''Homo sapiens'' IL-10 protein bound (retrieved from PDB 2h24, Yoon et al. 2006), with both p35 (chain A) and p40 (chain B) chains. This is a jmol applet, in which you can interactively see the protein format:
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<br>
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<div align="center">
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<html>
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<script src="http://www.cbi.cnptia.embrapa.br/jmol/Jmol.js" type="text/javascript"></script>
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<script type="text/javascript">
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  jmolInitialize("http://www.cbi.cnptia.embrapa.br/jmol/");
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  jmolApplet(400, "load http://www.cbi.cnptia.embrapa.br/jmol/files/2h24.pdb;");
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  jmolBr();
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jmolButton("restrict not dna; restrict not protein; restrict not HOH; restrict not ligand; dots off; selectionhalos off; center selected; zoom 100; select all; wireframe; select all; color chain; select Cu or Cu1 or Zn or fe or Ca or Cl or Mn or Mg or na or Br or SO4 or ligand; color magenta selected; cpk; select all", "Stick view", "Stick view")
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jmolButton("restrict not HOH; select all; wireframe off;dots off; ribbon; color structure; zoom 100;  center selected; label off; backbone off; selectionhalos off; color structure; select Cu or Cu1 or Zn or fe or Ca or Cl or Mn or Mg or na or Br or SO4 or ligand; cpk; select ligand; wireframe 75; select all; Hbonds off; SSbonds off; select ligand; ribbon off", "Ribbon view", "Ribbon view")
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jmolButton("restrict not dna; restrict not protein; restrict not HOH; restrict not ligand; dots off; selectionhalos off; center selected; zoom 100; select all; wireframe; select all; color chain; backbone 50; wireframe off; select Cu or Cu1 or Zn or fe or Ca or Cl or Mn or Mg or na or Br or SO4 or ligand; cpk; select ligand; wireframe 75; select all; Hbonds off; SSbonds off; select ligand; backbone off", "Wireframe view", "Wireframe view")
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  jmolButton("spin y" ,"spin y");
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  jmolButton("spin off" ,"spin off");
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</script>
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</div>
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<br />
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</html>
  
  
 
===References===
 
===References===
  
−
Steidler L, Hans W, Schotte L, Neirynck S, Obermeier F, Falk W, Fiers W, Remaut E. Treatment of murine colitis by Lactococcus lactis secreting interleukin-10, Science 289. 2000. 1352–1355. [http://www.ncbi.nlm.nih.gov/pubmed/10958782 Link to Pubmed]
+
#Steidler L, Hans W, Schotte L, Neirynck S, Obermeier F, Falk W, Fiers W, Remaut E. Treatment of murine colitis by Lactococcus lactis secreting interleukin-10, Science 289. 2000. 1352–1355. [http://www.ncbi.nlm.nih.gov/pubmed/10958782 Link to Pubmed]
 +
#Yoon, S.I.,  Logsdon, N.J.,  Sheikh, F.,  Donnelly, R.P.,  Walter, M.R. Conformational changes mediate interleukin-10 receptor 2 (IL-10R2) binding to IL-10 and assembly of the signaling complex. Journal: (2006) J.Biol.Chem. 281: 35088-35096 [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=16982608 Link to PubMed]

Revision as of 01:48, 27 September 2011

IL10

IL-10 is an anti-inflammatory interleukin, produced mainly by monocytes. It is responsible for down-regulating the synthesis of pro-inflammatory cytokines like IFN-γ, IL-2, IL-3, TNFα (Th1 cytokines), class II MHC, and co-stimulatory molecules on macrophages. IL-10 also displays potent abilities to suppress the antigen presentation capacity of APCs (Antigen Presenting Cells), and it is also responsible for enhancing B cell survival, proliferation and antibody secretion. In this scenario IL-10 favors Th2 response (Mocellin et al 2004, Elenkov & Chrousos, 1999).

Some studies suggested that IL-10 acts as immunoregulator in intestinal tract. For example Steidler et al (2000) used a genetically modified Lactococcus lacti expressing IL-10 to treat mice with Inflammatory Bowel Disease (IBD), and the inflammatory response signals were reduced in 50%. IBD is an autoimmune disease which, unlike the immune response found in intestinal tract due to stress, involves a Th1 polarization and inflammation.

Sequence and Features


Assembly Compatibility:
  • 10
    COMPATIBLE WITH RFC[10]
  • 12
    COMPATIBLE WITH RFC[12]
  • 21
    COMPATIBLE WITH RFC[21]
  • 23
    COMPATIBLE WITH RFC[23]
  • 25
    COMPATIBLE WITH RFC[25]
  • 1000
    COMPATIBLE WITH RFC[1000]


Usage and Biology

This part is used by [http://2011.igem.org/Team:UNICAMP-EMSE_Brazil UNICAMP-EMSE Brazil team] as the final product of the [http://2011.igem.org/Team:UNICAMP-EMSE_Brazil/Project#Device_2:_NO_sensor.2FIL-10_producer NO sensor device/ IL-10 producer] ("Device 2", which senses NO levels and responds by producing and secreting IL-10. This part is shown as green in the following schema:

UNICAMP EMSE NO device schema.jpg

The team chooses IL-10 to impair inflammatory response mediated by Th1 overstimulation (due to Device 1 action), to reach an equilibrium between immune stimulation (Th1) and suppression (Th2).

In the folllowing schema you can have a more detailed view of the [http://2011.igem.org/Team:UNICAMP-EMSE_Brazil/Project#Device_2:_NO_sensor.2FIL-10_producer NO sensor device/ IL-10 producer] ("Device 2") functioning:

700px


Three-dimensional structure representation

You can find below a tridimensional structure of Homo sapiens IL-10 protein bound (retrieved from PDB 2h24, Yoon et al. 2006), with both p35 (chain A) and p40 (chain B) chains. This is a jmol applet, in which you can interactively see the protein format:



References

  1. Steidler L, Hans W, Schotte L, Neirynck S, Obermeier F, Falk W, Fiers W, Remaut E. Treatment of murine colitis by Lactococcus lactis secreting interleukin-10, Science 289. 2000. 1352–1355. [http://www.ncbi.nlm.nih.gov/pubmed/10958782 Link to Pubmed]
  2. Yoon, S.I., Logsdon, N.J., Sheikh, F., Donnelly, R.P., Walter, M.R. Conformational changes mediate interleukin-10 receptor 2 (IL-10R2) binding to IL-10 and assembly of the signaling complex. Journal: (2006) J.Biol.Chem. 281: 35088-35096 [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=16982608 Link to PubMed]