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| | <StructureSection load='1y6k' size='340' side='right'caption='[[1y6k]], [[Resolution|resolution]] 2.52Å' scene=''> | | <StructureSection load='1y6k' size='340' side='right'caption='[[1y6k]], [[Resolution|resolution]] 2.52Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1y6k]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1Y6K OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=1Y6K FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1y6k]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1Y6K OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1Y6K FirstGlance]. <br> |
| | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1j7v|1j7v]], [[1y6m|1y6m]], [[1y6n|1y6n]]</div></td></tr> | | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1j7v|1j7v]], [[1y6m|1y6m]], [[1y6n|1y6n]]</div></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">IL10 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), IL10RA, IL10R ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">IL10 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), IL10RA, IL10R ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=1y6k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1y6k OCA], [http://pdbe.org/1y6k PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1y6k RCSB], [http://www.ebi.ac.uk/pdbsum/1y6k PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1y6k ProSAT]</span></td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1y6k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1y6k OCA], [https://pdbe.org/1y6k PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1y6k RCSB], [https://www.ebi.ac.uk/pdbsum/1y6k PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1y6k ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/I10R1_HUMAN I10R1_HUMAN]] Defects in IL10RA are the cause of inflammatory bowel disease type 28 (IBD28) [MIM:[http://omim.org/entry/613148 613148]]. It is a chronic, relapsing inflammation of the gastrointestinal tract with a complex etiology. It is subdivided into Crohn disease and ulcerative colitis phenotypes. Crohn disease may affect any part of the gastrointestinal tract from the mouth to the anus, but most frequently it involves the terminal ileum and colon. Bowel inflammation is transmural and discontinuous; it may contain granulomas or be associated with intestinal or perianal fistulas. In contrast, in ulcerative colitis, the inflammation is continuous and limited to rectal and colonic mucosal layers; fistulas and granulomas are not observed. Both diseases include extraintestinal inflammation of the skin, eyes, or joints.<ref>PMID:19890111</ref> | + | [[https://www.uniprot.org/uniprot/I10R1_HUMAN I10R1_HUMAN]] Defects in IL10RA are the cause of inflammatory bowel disease type 28 (IBD28) [MIM:[https://omim.org/entry/613148 613148]]. It is a chronic, relapsing inflammation of the gastrointestinal tract with a complex etiology. It is subdivided into Crohn disease and ulcerative colitis phenotypes. Crohn disease may affect any part of the gastrointestinal tract from the mouth to the anus, but most frequently it involves the terminal ileum and colon. Bowel inflammation is transmural and discontinuous; it may contain granulomas or be associated with intestinal or perianal fistulas. In contrast, in ulcerative colitis, the inflammation is continuous and limited to rectal and colonic mucosal layers; fistulas and granulomas are not observed. Both diseases include extraintestinal inflammation of the skin, eyes, or joints.<ref>PMID:19890111</ref> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/IL10_HUMAN IL10_HUMAN]] Inhibits the synthesis of a number of cytokines, including IFN-gamma, IL-2, IL-3, TNF and GM-CSF produced by activated macrophages and by helper T-cells. [[http://www.uniprot.org/uniprot/I10R1_HUMAN I10R1_HUMAN]] Receptor for IL10; binds IL10 with a high affinity. | + | [[https://www.uniprot.org/uniprot/IL10_HUMAN IL10_HUMAN]] Inhibits the synthesis of a number of cytokines, including IFN-gamma, IL-2, IL-3, TNF and GM-CSF produced by activated macrophages and by helper T-cells. [[https://www.uniprot.org/uniprot/I10R1_HUMAN I10R1_HUMAN]] Receptor for IL10; binds IL10 with a high affinity. |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| Structural highlights
Disease
[I10R1_HUMAN] Defects in IL10RA are the cause of inflammatory bowel disease type 28 (IBD28) [MIM:613148]. It is a chronic, relapsing inflammation of the gastrointestinal tract with a complex etiology. It is subdivided into Crohn disease and ulcerative colitis phenotypes. Crohn disease may affect any part of the gastrointestinal tract from the mouth to the anus, but most frequently it involves the terminal ileum and colon. Bowel inflammation is transmural and discontinuous; it may contain granulomas or be associated with intestinal or perianal fistulas. In contrast, in ulcerative colitis, the inflammation is continuous and limited to rectal and colonic mucosal layers; fistulas and granulomas are not observed. Both diseases include extraintestinal inflammation of the skin, eyes, or joints.[1]
Function
[IL10_HUMAN] Inhibits the synthesis of a number of cytokines, including IFN-gamma, IL-2, IL-3, TNF and GM-CSF produced by activated macrophages and by helper T-cells. [I10R1_HUMAN] Receptor for IL10; binds IL10 with a high affinity.
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Human IL-10 (hIL-10) is a cytokine that modulates diverse immune responses. The Epstein-Barr virus (EBV) genome contains an IL-10 homolog (vIL-10) that shares high sequence and structural similarity with hIL-10. Although vIL-10 suppresses inflammatory responses like hIL-10, it cannot activate many other immunostimulatory functions performed by the cellular cytokine. These functional differences have been correlated with the approximately 1000-fold lower affinity of vIL-10, compared to hIL-10, for the IL-10R1 receptor chain. To define the structural basis for these observations, crystal structures of vIL-10 and a vIL-10 point mutant were determined bound to the soluble IL-10R1 receptor fragment (sIL-10R1) at 2.8 and 2.7 A resolution, respectively. The structures reveal that subtle changes in the conformation and dynamics of the vIL-10 AB and CD loops and an orientation change of vIL-10 on sIL-10R1 are the main factors responsible for vIL-10's reduced affinity for sIL-10R1 and its distinct biological profile.
Same structure, different function crystal structure of the Epstein-Barr virus IL-10 bound to the soluble IL-10R1 chain.,Yoon SI, Jones BC, Logsdon NJ, Walter MR Structure. 2005 Apr;13(4):551-64. PMID:15837194[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Glocker EO, Kotlarz D, Boztug K, Gertz EM, Schaffer AA, Noyan F, Perro M, Diestelhorst J, Allroth A, Murugan D, Hatscher N, Pfeifer D, Sykora KW, Sauer M, Kreipe H, Lacher M, Nustede R, Woellner C, Baumann U, Salzer U, Koletzko S, Shah N, Segal AW, Sauerbrey A, Buderus S, Snapper SB, Grimbacher B, Klein C. Inflammatory bowel disease and mutations affecting the interleukin-10 receptor. N Engl J Med. 2009 Nov 19;361(21):2033-45. doi: 10.1056/NEJMoa0907206. Epub 2009 , Nov 4. PMID:19890111 doi:10.1056/NEJMoa0907206
- ↑ Yoon SI, Jones BC, Logsdon NJ, Walter MR. Same structure, different function crystal structure of the Epstein-Barr virus IL-10 bound to the soluble IL-10R1 chain. Structure. 2005 Apr;13(4):551-64. PMID:15837194 doi:10.1016/j.str.2005.01.016
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