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| - | {{STRUCTURE_1lqs| PDB=1lqs | SCENE= }}
| + | ==CRYSTAL STRUCTURE OF HUMAN CYTOMEGALOVIRUS IL-10 BOUND TO SOLUBLE HUMAN IL-10R1== |
| - | ===CRYSTAL STRUCTURE OF HUMAN CYTOMEGALOVIRUS IL-10 BOUND TO SOLUBLE HUMAN IL-10R1===
| + | <StructureSection load='1lqs' size='340' side='right' caption='[[1lqs]], [[Resolution|resolution]] 2.70Å' scene=''> |
| - | {{ABSTRACT_PUBMED_12093920}}
| + | == Structural highlights == |
| | + | <table><tr><td colspan='2'>[[1lqs]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Human_herpesvirus_5 Human herpesvirus 5]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1LQS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1LQS FirstGlance]. <br> |
| | + | </td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene><br> |
| | + | <tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1j7v|1j7v]]</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=1lqs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1lqs OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1lqs RCSB], [http://www.ebi.ac.uk/pdbsum/1lqs 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/I10R1_HUMAN I10R1_HUMAN]] Receptor for IL10; binds IL10 with a high affinity. [[http://www.uniprot.org/uniprot/IL10H_HCMVA IL10H_HCMVA]] Functional viral IL-10 homolog. Can bind to the human IL-10 receptor and compete with human IL-10 for binding sites. Requires both subunits of the human IL-10 receptor complex to induce signal transduction events and biological activities. IL-10 signaling pathway has several immunosuppressive activities that are exploited by the virus. Inhibits TLR-induced type I interferon production in host plasmacytoid dendritic cells.<ref>PMID:15280480</ref> <ref>PMID:19524994</ref> |
| | + | == 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/lq/1lqs_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) modulates critical immune and inflammatory responses by way of interactions with its high- (IL-10R1) and low-affinity (IL-10R2) cell surface receptors. Human cytomegalovirus exploits the IL-10 signaling pathway by expressing a functional viral IL-10 homolog (cmvIL-10), which shares only 27% sequence identity with hIL-10 yet signals through IL-10R1 and IL-10R2. To define the molecular basis of this virus-host interaction, we determined the 2.7-A crystal structure of cmvIL-10 bound to the extracellular fragment of IL-10R1 (sIL-10R1). The structure reveals cmvIL-10 forms a disulfide-linked homodimer that binds two sIL-10R1 molecules. Although cmvIL-10 and hIL-10 share similar intertwined topologies and sIL-10R1 binding sites, their respective interdomain angles differ by approximately 40 degrees. This difference results in a striking re-organization of the IL-10R1s in the putative cell surface complex. Solution binding studies show cmvIL-10 and hIL-10 share essentially identical affinities for sIL-10R1 whereas the Epstein-Barr virus IL-10 homolog (ebvIL-10), whose structure is highly similar to hIL-10, exhibits a approximately 20-fold reduction in sIL-10R1 affinity. Our results suggest cmvIL-10 and ebvIL-10 have evolved different molecular mechanisms to engage the IL-10 receptors that ultimately enhance the respective ability of their virus to escape immune detection. |
| | | | |
| - | ==Disease==
| + | Crystal structure of human cytomegalovirus IL-10 bound to soluble human IL-10R1.,Jones BC, Logsdon NJ, Josephson K, Cook J, Barry PA, Walter MR Proc Natl Acad Sci U S A. 2002 Jul 9;99(14):9404-9. Epub 2002 Jul 1. PMID:12093920<ref>PMID:12093920</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/I10R1_HUMAN I10R1_HUMAN]] Receptor for IL10; binds IL10 with a high affinity. [[http://www.uniprot.org/uniprot/IL10H_HCMVA IL10H_HCMVA]] Functional viral IL-10 homolog. Can bind to the human IL-10 receptor and compete with human IL-10 for binding sites. Requires both subunits of the human IL-10 receptor complex to induce signal transduction events and biological activities. IL-10 signaling pathway has several immunosuppressive activities that are exploited by the virus. Inhibits TLR-induced type I interferon production in host plasmacytoid dendritic cells.<ref>PMID:15280480</ref><ref>PMID:19524994</ref>
| + | </div> |
| - | | + | |
| - | ==About this Structure==
| + | |
| - | [[1lqs]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Human_herpesvirus_5 Human herpesvirus 5]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1LQS OCA].
| + | |
| | | | |
| | ==See Also== | | ==See Also== |
| | *[[Interleukin|Interleukin]] | | *[[Interleukin|Interleukin]] |
| | *[[Interleukin receptor|Interleukin receptor]] | | *[[Interleukin receptor|Interleukin receptor]] |
| - | | + | == References == |
| - | ==Reference== | + | <references/> |
| - | <ref group="xtra">PMID:012093920</ref><references group="xtra"/><references/>
| + | __TOC__ |
| | + | </StructureSection> |
| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| | [[Category: Human herpesvirus 5]] | | [[Category: Human herpesvirus 5]] |
| Structural highlights
1lqs is a 4 chain structure with sequence from Homo sapiens and Human herpesvirus 5. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: |
| | Related: | 1j7v |
| 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
[I10R1_HUMAN] Receptor for IL10; binds IL10 with a high affinity. [IL10H_HCMVA] Functional viral IL-10 homolog. Can bind to the human IL-10 receptor and compete with human IL-10 for binding sites. Requires both subunits of the human IL-10 receptor complex to induce signal transduction events and biological activities. IL-10 signaling pathway has several immunosuppressive activities that are exploited by the virus. Inhibits TLR-induced type I interferon production in host plasmacytoid dendritic cells.[2] [3]
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) modulates critical immune and inflammatory responses by way of interactions with its high- (IL-10R1) and low-affinity (IL-10R2) cell surface receptors. Human cytomegalovirus exploits the IL-10 signaling pathway by expressing a functional viral IL-10 homolog (cmvIL-10), which shares only 27% sequence identity with hIL-10 yet signals through IL-10R1 and IL-10R2. To define the molecular basis of this virus-host interaction, we determined the 2.7-A crystal structure of cmvIL-10 bound to the extracellular fragment of IL-10R1 (sIL-10R1). The structure reveals cmvIL-10 forms a disulfide-linked homodimer that binds two sIL-10R1 molecules. Although cmvIL-10 and hIL-10 share similar intertwined topologies and sIL-10R1 binding sites, their respective interdomain angles differ by approximately 40 degrees. This difference results in a striking re-organization of the IL-10R1s in the putative cell surface complex. Solution binding studies show cmvIL-10 and hIL-10 share essentially identical affinities for sIL-10R1 whereas the Epstein-Barr virus IL-10 homolog (ebvIL-10), whose structure is highly similar to hIL-10, exhibits a approximately 20-fold reduction in sIL-10R1 affinity. Our results suggest cmvIL-10 and ebvIL-10 have evolved different molecular mechanisms to engage the IL-10 receptors that ultimately enhance the respective ability of their virus to escape immune detection.
Crystal structure of human cytomegalovirus IL-10 bound to soluble human IL-10R1.,Jones BC, Logsdon NJ, Josephson K, Cook J, Barry PA, Walter MR Proc Natl Acad Sci U S A. 2002 Jul 9;99(14):9404-9. Epub 2002 Jul 1. PMID:12093920[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
- ↑ Chang WL, Baumgarth N, Yu D, Barry PA. Human cytomegalovirus-encoded interleukin-10 homolog inhibits maturation of dendritic cells and alters their functionality. J Virol. 2004 Aug;78(16):8720-31. PMID:15280480 doi:10.1128/JVI.78.16.8720-8731.2004
- ↑ Chang WL, Barry PA, Szubin R, Wang D, Baumgarth N. Human cytomegalovirus suppresses type I interferon secretion by plasmacytoid dendritic cells through its interleukin 10 homolog. Virology. 2009 Aug 1;390(2):330-7. doi: 10.1016/j.virol.2009.05.013. Epub 2009, Jun 13. PMID:19524994 doi:10.1016/j.virol.2009.05.013
- ↑ Jones BC, Logsdon NJ, Josephson K, Cook J, Barry PA, Walter MR. Crystal structure of human cytomegalovirus IL-10 bound to soluble human IL-10R1. Proc Natl Acad Sci U S A. 2002 Jul 9;99(14):9404-9. Epub 2002 Jul 1. PMID:12093920 doi:10.1073/pnas.152147499
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