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| | ==Crystal structure of an Interleukin-1 receptor complex== | | ==Crystal structure of an Interleukin-1 receptor complex== |
| - | <StructureSection load='3o4o' size='340' side='right' caption='[[3o4o]], [[Resolution|resolution]] 3.30Å' scene=''> | + | <StructureSection load='3o4o' size='340' side='right'caption='[[3o4o]], [[Resolution|resolution]] 3.30Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3o4o]] is a 3 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=3O4O OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3O4O FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3o4o]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3O4O OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3O4O FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.3Å</td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3o4o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3o4o OCA], [http://pdbe.org/3o4o PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3o4o RCSB], [http://www.ebi.ac.uk/pdbsum/3o4o PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3o4o ProSAT]</span></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></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=3o4o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3o4o OCA], [https://pdbe.org/3o4o PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3o4o RCSB], [https://www.ebi.ac.uk/pdbsum/3o4o PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3o4o ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/IL1B_HUMAN IL1B_HUMAN]] Produced by activated macrophages, IL-1 stimulates thymocyte proliferation by inducing IL-2 release, B-cell maturation and proliferation, and fibroblast growth factor activity. IL-1 proteins are involved in the inflammatory response, being identified as endogenous pyrogens, and are reported to stimulate the release of prostaglandin and collagenase from synovial cells.<ref>PMID:3920526</ref> [[http://www.uniprot.org/uniprot/IL1AP_HUMAN IL1AP_HUMAN]] Coreceptor with IL1R1. Associates with IL1R1 bound to IL1B to form the high affinity interleukin-1 receptor complex which mediates interleukin-1-dependent activation of NF-kappa-B and other pathways. Signaling involves the recruitment of adapter molecules such as TOLLIP, MYD88, and IRAK1 or IRAK2 via the respective TIR domains of the receptor/coreceptor subunits. Recruits TOLLIP to the signaling complex. Does not bind to interleukin-1 alone; binding of IL1RN to IL1R1, prevents its association with IL1R1 to form a signaling complex. The cellular response is modulated through a non-signaling association with the membrane IL1R2 decoy receptor. Secreted forms (isoforms 2 and 3) associate with secreted ligand-bound IL1R2 and increase the affinity of secreted IL1R2 for IL1B; this complex formation may be the dominant mechanism for neutralization of IL1B by secreted/soluble receptors.<ref>PMID:9371760</ref> <ref>PMID:10799889</ref> <ref>PMID:12530978</ref> [[http://www.uniprot.org/uniprot/IL1R2_HUMAN IL1R2_HUMAN]] Non-signaling receptor for IL1A, IL1B and IL1RN. Reduces IL1B activities. Serves as a decoy receptor by competetive binding to IL1B and preventing its binding to IL1R1. Also modulates cellular response through non-signaling association with IL1RAP after binding to IL1B. IL1R2 (membrane and secreted forms) preferentially binds IL1B and poorly IL1A and IL1RN. The secreted IL1R2 recruits secreted IL1RAP with high affinity; this complex formation may be the dominant mechanism for neutralization of IL1B by secreted/soluble receptors.<ref>PMID:10975853</ref> <ref>PMID:12530978</ref> <ref>PMID:7989776</ref> <ref>PMID:9862719</ref> | + | [https://www.uniprot.org/uniprot/IL1B_HUMAN IL1B_HUMAN] Produced by activated macrophages, IL-1 stimulates thymocyte proliferation by inducing IL-2 release, B-cell maturation and proliferation, and fibroblast growth factor activity. IL-1 proteins are involved in the inflammatory response, being identified as endogenous pyrogens, and are reported to stimulate the release of prostaglandin and collagenase from synovial cells.<ref>PMID:3920526</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | <jmolCheckbox> | | <jmolCheckbox> |
| | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/o4/3o4o_consurf.spt"</scriptWhenChecked> | | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/o4/3o4o_consurf.spt"</scriptWhenChecked> |
| - | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
| | </jmolCheckbox> | | </jmolCheckbox> |
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| | ==See Also== | | ==See Also== |
| - | *[[Interleukin|Interleukin]] | + | *[[Interleukin 3D structures|Interleukin 3D structures]] |
| - | *[[Interleukin receptor|Interleukin receptor]] | + | *[[Interleukin receptor 3D structures|Interleukin receptor 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Li, L]] | + | [[Category: Large Structures]] |
| - | [[Category: Liu, X]] | + | [[Category: Li L]] |
| - | [[Category: Mei, K R]]
| + | [[Category: Liu X]] |
| - | [[Category: Wang, D L]]
| + | [[Category: Mei KR]] |
| - | [[Category: Wang, X Q]] | + | [[Category: Wang DL]] |
| - | [[Category: Zhang, S Y]] | + | [[Category: Wang XQ]] |
| - | [[Category: Beta-trefoil]] | + | [[Category: Zhang SY]] |
| - | [[Category: Cytokine-receptor complex]] | + | |
| - | [[Category: Ig-like fold]] | + | |
| - | [[Category: Immune system]]
| + | |
| Structural highlights
Function
IL1B_HUMAN Produced by activated macrophages, IL-1 stimulates thymocyte proliferation by inducing IL-2 release, B-cell maturation and proliferation, and fibroblast growth factor activity. IL-1 proteins are involved in the inflammatory response, being identified as endogenous pyrogens, and are reported to stimulate the release of prostaglandin and collagenase from synovial cells.[1]
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 1beta (IL-1beta) is a key orchestrator of inflammation and host defense that exerts its effects through IL-1 receptor type I (IL-1RI) and IL-1 receptor accessory protein (IL-1RAcP). How IL-1RAcP is recruited by IL-1beta-IL-1RI to form the signaling-competent complex remains elusive. Here we present the crystal structure of IL-1beta bound to IL-1 receptor type II (IL-1RII) and IL-1RAcP. IL-1beta-IL-1RII generated a composite binding surface to recruit IL-1RAcP. Biochemical analysis demonstrated that IL-1beta-IL-1RI and IL-1beta-IL-1RII interacted similarly with IL-1RAcP. It also showed the importance of two loops of IL-1 receptor antagonist (IL-1Ra) in determining its antagonism. Our results provide a structural basis for assembly and activation of the IL-1 receptor and offer a general cytokine-receptor architecture that governs the IL-1 family of cytokines.
Structural insights into the assembly and activation of IL-1beta with its receptors.,Wang D, Zhang S, Li L, Liu X, Mei K, Wang X Nat Immunol. 2010 Aug 29. PMID:20802483[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Van Damme J, De Ley M, Opdenakker G, Billiau A, De Somer P, Van Beeumen J. Homogeneous interferon-inducing 22K factor is related to endogenous pyrogen and interleukin-1. Nature. 1985 Mar 21-27;314(6008):266-8. PMID:3920526
- ↑ Wang D, Zhang S, Li L, Liu X, Mei K, Wang X. Structural insights into the assembly and activation of IL-1beta with its receptors. Nat Immunol. 2010 Aug 29. PMID:20802483 doi:10.1038/ni.1925
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