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==Solution structure of human interleukin-33== | |||
<StructureSection load='2kll' size='340' side='right'caption='[[2kll]]' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[2kll]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2KLL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2KLL FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</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=2kll FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2kll OCA], [https://pdbe.org/2kll PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2kll RCSB], [https://www.ebi.ac.uk/pdbsum/2kll PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2kll ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/IL33_HUMAN IL33_HUMAN] Cytokine that binds to and signals through IL1RL1/ST2 and its stimulation recruits MYD88, IRAK1, IRAK4, and TRAF6, followed by phosphorylation of MAPK3/ERK1 and/or MAPK1/ERK2, MAPK14, and MAPK8. Induces T-helper type 2-associated cytokines. Acts as a chemoattractant tor Th2 cells, and may function as an "alarmin", that amplifies immune responses during tissue injury.<ref>PMID:16286016</ref> <ref>PMID:17853410</ref> <ref>PMID:17185418</ref> <ref>PMID:18787100</ref> <ref>PMID:18836528</ref> <ref>PMID:21734074</ref> <ref>PMID:22215666</ref> In quiescent endothelia the uncleaved form is constitutively and abundantly expressed, and acts as a chromatin-associated nuclear factor with transcriptional repressor properties, it may sequester nuclear NF-kappaB/RELA, lowering expression of its targets. This form is rapidely lost upon angiogenic or proinflammatory activation.<ref>PMID:16286016</ref> <ref>PMID:17853410</ref> <ref>PMID:17185418</ref> <ref>PMID:18787100</ref> <ref>PMID:18836528</ref> <ref>PMID:21734074</ref> <ref>PMID:22215666</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Members of the interleukin-1 (IL-1) family of cytokines play major roles in host defense and immune system regulation in infectious and inflammatory diseases. IL-1 cytokines trigger a biological response in effector cells by assembling a heterotrimeric signaling complex with two IL-1 receptor chains, a high-affinity primary receptor and a low-affinity coreceptor. To gain insights into the signaling mechanism of the novel IL-1-like cytokine IL-33, we first solved its solution structure and then performed a detailed biochemical and structural characterization of the interaction between IL-33, its primary receptor ST2, and the coreceptor IL-1RAcP. Using nuclear magnetic resonance data, we obtained a model of the IL-33/ST2 complex in solution that is validated by small-angle X-ray scattering (SAXS) data and is similar to the IL-1beta/IL-1R1 complex. We extended our SAXS analysis to the IL-33/ST2/IL-1RAcP and IL-1beta/IL-1R1/IL-1RAcP complexes and propose a general model of the molecular architecture of IL-1 ternary signaling complexes. | |||
Structure of IL-33 and its interaction with the ST2 and IL-1RAcP receptors--insight into heterotrimeric IL-1 signaling complexes.,Lingel A, Weiss TM, Niebuhr M, Pan B, Appleton BA, Wiesmann C, Bazan JF, Fairbrother WJ Structure. 2009 Oct 14;17(10):1398-410. PMID:19836339<ref>PMID:19836339</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 2kll" style="background-color:#fffaf0;"></div> | |||
==See Also== | ==See Also== | ||
*[[Interleukin|Interleukin]] | *[[Interleukin 3D structures|Interleukin 3D structures]] | ||
== References == | |||
== | <references/> | ||
< | __TOC__ | ||
</StructureSection> | |||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: | [[Category: Fairbrother W]] | ||
[[Category: | [[Category: Lingel A]] | ||
Latest revision as of 12:49, 9 May 2024
Solution structure of human interleukin-33Solution structure of human interleukin-33
Structural highlights
FunctionIL33_HUMAN Cytokine that binds to and signals through IL1RL1/ST2 and its stimulation recruits MYD88, IRAK1, IRAK4, and TRAF6, followed by phosphorylation of MAPK3/ERK1 and/or MAPK1/ERK2, MAPK14, and MAPK8. Induces T-helper type 2-associated cytokines. Acts as a chemoattractant tor Th2 cells, and may function as an "alarmin", that amplifies immune responses during tissue injury.[1] [2] [3] [4] [5] [6] [7] In quiescent endothelia the uncleaved form is constitutively and abundantly expressed, and acts as a chromatin-associated nuclear factor with transcriptional repressor properties, it may sequester nuclear NF-kappaB/RELA, lowering expression of its targets. This form is rapidely lost upon angiogenic or proinflammatory activation.[8] [9] [10] [11] [12] [13] [14] Publication Abstract from PubMedMembers of the interleukin-1 (IL-1) family of cytokines play major roles in host defense and immune system regulation in infectious and inflammatory diseases. IL-1 cytokines trigger a biological response in effector cells by assembling a heterotrimeric signaling complex with two IL-1 receptor chains, a high-affinity primary receptor and a low-affinity coreceptor. To gain insights into the signaling mechanism of the novel IL-1-like cytokine IL-33, we first solved its solution structure and then performed a detailed biochemical and structural characterization of the interaction between IL-33, its primary receptor ST2, and the coreceptor IL-1RAcP. Using nuclear magnetic resonance data, we obtained a model of the IL-33/ST2 complex in solution that is validated by small-angle X-ray scattering (SAXS) data and is similar to the IL-1beta/IL-1R1 complex. We extended our SAXS analysis to the IL-33/ST2/IL-1RAcP and IL-1beta/IL-1R1/IL-1RAcP complexes and propose a general model of the molecular architecture of IL-1 ternary signaling complexes. Structure of IL-33 and its interaction with the ST2 and IL-1RAcP receptors--insight into heterotrimeric IL-1 signaling complexes.,Lingel A, Weiss TM, Niebuhr M, Pan B, Appleton BA, Wiesmann C, Bazan JF, Fairbrother WJ Structure. 2009 Oct 14;17(10):1398-410. PMID:19836339[15] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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