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| - | {{STRUCTURE_1y6n| PDB=1y6n | SCENE= }}
| + | ==Crystal structure of Epstein-Barr virus IL-10 mutant (A87I) complexed with the soluble IL-10R1 chain== |
| - | ===Crystal structure of Epstein-Barr virus IL-10 mutant (A87I) complexed with the soluble IL-10R1 chain===
| + | <StructureSection load='1y6n' size='340' side='right' caption='[[1y6n]], [[Resolution|resolution]] 2.70Å' scene=''> |
| - | {{ABSTRACT_PUBMED_15837194}}
| + | == Structural highlights == |
| | + | <table><tr><td colspan='2'>[[1y6n]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Human_herpesvirus_4 Human herpesvirus 4]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1Y6N OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1Y6N FirstGlance]. <br> |
| | + | </td></tr><tr><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr> |
| | + | <tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1y6k|1y6k]], [[1j7v|1j7v]], [[1y6m|1y6m]]</td></tr> |
| | + | <tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">BCRF1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10376 Human herpesvirus 4]), IL10RA, IL10R ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</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=1y6n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1y6n OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1y6n RCSB], [http://www.ebi.ac.uk/pdbsum/1y6n 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/IL10H_EBV IL10H_EBV]] Plays a role in masking infected cells for immune recognition by cytotoxic T-lymphocytes. Down-regulates the expression of the host TAP1 gene (transporter associated with antigen processing), thereby affecting the transport of peptides into the endoplasmic reticulum and subsequent peptide loading by MHC class I molecules. Inhibits IFN-gamma synthesis.<ref>PMID:2161559</ref> <ref>PMID:9310490</ref> [[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/y6/1y6n_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 == |
| | + | 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. |
| | | | |
| - | ==Disease==
| + | 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<ref>PMID:15837194</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/IL10H_EBV IL10H_EBV]] Plays a role in masking infected cells for immune recognition by cytotoxic T-lymphocytes. Down-regulates the expression of the host TAP1 gene (transporter associated with antigen processing), thereby affecting the transport of peptides into the endoplasmic reticulum and subsequent peptide loading by MHC class I molecules. Inhibits IFN-gamma synthesis.<ref>PMID:2161559</ref><ref>PMID:9310490</ref> [[http://www.uniprot.org/uniprot/I10R1_HUMAN I10R1_HUMAN]] Receptor for IL10; binds IL10 with a high affinity.
| + | </div> |
| - | | + | |
| - | ==About this Structure==
| + | |
| - | [[1y6n]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Human_herpesvirus_4 Human herpesvirus 4]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1Y6N OCA].
| + | |
| | | | |
| | ==See Also== | | ==See Also== |
| | *[[Interleukin|Interleukin]] | | *[[Interleukin|Interleukin]] |
| | *[[Interleukin receptor|Interleukin receptor]] | | *[[Interleukin receptor|Interleukin receptor]] |
| - | | + | == References == |
| - | ==Reference== | + | <references/> |
| - | <ref group="xtra">PMID:015837194</ref><references group="xtra"/><references/>
| + | __TOC__ |
| | + | </StructureSection> |
| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| | [[Category: Human herpesvirus 4]] | | [[Category: Human herpesvirus 4]] |
| Structural highlights
1y6n is a 2 chain structure with sequence from Homo sapiens and Human herpesvirus 4. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | NonStd Res: | |
| Related: | 1y6k, 1j7v, 1y6m |
| Gene: | BCRF1 (Human herpesvirus 4), IL10RA, IL10R (Homo sapiens) |
| 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
[IL10H_EBV] Plays a role in masking infected cells for immune recognition by cytotoxic T-lymphocytes. Down-regulates the expression of the host TAP1 gene (transporter associated with antigen processing), thereby affecting the transport of peptides into the endoplasmic reticulum and subsequent peptide loading by MHC class I molecules. Inhibits IFN-gamma synthesis.[2] [3] [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[4]
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
- ↑ Moore KW, Vieira P, Fiorentino DF, Trounstine ML, Khan TA, Mosmann TR. Homology of cytokine synthesis inhibitory factor (IL-10) to the Epstein-Barr virus gene BCRFI. Science. 1990 Jun 8;248(4960):1230-4. PMID:2161559
- ↑ Zeidler R, Eissner G, Meissner P, Uebel S, Tampe R, Lazis S, Hammerschmidt W. Downregulation of TAP1 in B lymphocytes by cellular and Epstein-Barr virus-encoded interleukin-10. Blood. 1997 Sep 15;90(6):2390-7. PMID:9310490
- ↑ 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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