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| - | {{STRUCTURE_1j7v| PDB=1j7v | SCENE= }}
| + | ==HUMAN IL-10 / IL-10R1 COMPLEX== |
| - | ===HUMAN IL-10 / IL-10R1 COMPLEX=== | + | <StructureSection load='1j7v' size='340' side='right' caption='[[1j7v]], [[Resolution|resolution]] 2.90Å' scene=''> |
| - | {{ABSTRACT_PUBMED_11485736}}
| + | == Structural highlights == |
| | + | <table><tr><td colspan='2'>[[1j7v]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1J7V OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1J7V FirstGlance]. <br> |
| | + | </td></tr><tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1j7v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1j7v OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1j7v RCSB], [http://www.ebi.ac.uk/pdbsum/1j7v PDBsum]</span></td></tr> |
| | + | <table> |
| | + | == 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> |
| | + | == 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. |
| | + | == Evolutionary Conservation == |
| | + | [[Image:Consurf_key_small.gif|200px|right]] |
| | + | Check<jmol> |
| | + | <jmolCheckbox> |
| | + | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/j7/1j7v_consurf.spt"</scriptWhenChecked> |
| | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
| | + | <text>to colour the structure by Evolutionary Conservation</text> |
| | + | </jmolCheckbox> |
| | + | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf]. |
| | + | <div style="clear:both"></div> |
| | + | <div style="background-color:#fffaf0;"> |
| | + | == Publication Abstract from PubMed == |
| | + | Interleukin 10 (IL-10) is a dimeric cytokine that plays a central role in suppressing inflammatory responses. These activities are dependent on the interaction of IL-10 with its high-affinity receptor (IL-10R1). This intermediate complex must subsequently recruit the low-affinity IL-10R2 chain before cell signaling can occur. Here we report the 2.9 A crystal structure of IL-10 bound to a soluble form of IL-10R1 (sIL-10R1). The complex consists of two IL-10s and four sIL-10R1 molecules. Several residues in the IL-10/sIL-10R1 interface are conserved in all IL-10 homologs and their receptors. The data suggests that formation of the active IL-10 signaling complex occurs by a novel molecular recognition paradigm where IL-10R1 and IL-10R2 both recognize the same binding site on IL-10. |
| | | | |
| - | ==Disease==
| + | Crystal structure of the IL-10/IL-10R1 complex reveals a shared receptor binding site.,Josephson K, Logsdon NJ, Walter MR Immunity. 2001 Jul;15(1):35-46. PMID:11485736<ref>PMID:11485736</ref> |
| - | [[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>
| + | |
| | | | |
| - | ==Function==
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| - | [[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.
| + | </div> |
| - | | + | |
| - | ==About this Structure==
| + | |
| - | [[1j7v]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1J7V OCA].
| + | |
| | | | |
| | ==See Also== | | ==See Also== |
| | *[[Interleukin|Interleukin]] | | *[[Interleukin|Interleukin]] |
| | *[[Interleukin receptor|Interleukin receptor]] | | *[[Interleukin receptor|Interleukin receptor]] |
| - | | + | == References == |
| - | ==Reference== | + | <references/> |
| - | <ref group="xtra">PMID:011485736</ref><references group="xtra"/><references/>
| + | __TOC__ |
| | + | </StructureSection> |
| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| | [[Category: Josephson, K.]] | | [[Category: Josephson, K.]] |
| Structural highlights
1j7v is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Resources: | FirstGlance, OCA, RCSB, PDBsum |
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
Interleukin 10 (IL-10) is a dimeric cytokine that plays a central role in suppressing inflammatory responses. These activities are dependent on the interaction of IL-10 with its high-affinity receptor (IL-10R1). This intermediate complex must subsequently recruit the low-affinity IL-10R2 chain before cell signaling can occur. Here we report the 2.9 A crystal structure of IL-10 bound to a soluble form of IL-10R1 (sIL-10R1). The complex consists of two IL-10s and four sIL-10R1 molecules. Several residues in the IL-10/sIL-10R1 interface are conserved in all IL-10 homologs and their receptors. The data suggests that formation of the active IL-10 signaling complex occurs by a novel molecular recognition paradigm where IL-10R1 and IL-10R2 both recognize the same binding site on IL-10.
Crystal structure of the IL-10/IL-10R1 complex reveals a shared receptor binding site.,Josephson K, Logsdon NJ, Walter MR Immunity. 2001 Jul;15(1):35-46. PMID:11485736[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
- ↑ Josephson K, Logsdon NJ, Walter MR. Crystal structure of the IL-10/IL-10R1 complex reveals a shared receptor binding site. Immunity. 2001 Jul;15(1):35-46. PMID:11485736
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