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4kc3

From Proteopedia

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Cytokine/receptor binary complex

Structural highlights

4kc3 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.
Method:	X-ray diffraction, Resolution 3.2702Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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.^[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 PubMed

Interleukin (IL)-33 is an important member of the IL-1 family that has pleiotropic activities in innate and adaptive immune responses in host defense and disease. It signals through its ligand-binding primary receptor ST2 and IL-1 receptor accessory protein (IL-1RAcP), both of which are members of the IL-1 receptor family. To clarify the interaction of IL-33 with its receptors, we determined the crystal structure of IL-33 in complex with the ectodomain of ST2 at a resolution of 3.27 A. Coupled with structure-based mutagenesis and binding assay, the structural results define the molecular mechanism by which ST2 specifically recognizes IL-33. Structural comparison with other ligand-receptor complexes in the IL-1 family indicates that surface-charge complementarity is critical in determining ligand-binding specificity of IL-1 primary receptors. Combined crystallography and small-angle X-ray-scattering studies reveal that ST2 possesses hinge flexibility between the D3 domain and D1D2 module, whereas IL-1RAcP exhibits a rigid conformation in the unbound state in solution. The molecular flexibility of ST2 provides structural insights into domain-level conformational change of IL-1 primary receptors upon ligand binding, and the rigidity of IL-1RAcP explains its inability to bind ligands directly. The solution architecture of IL-33-ST2-IL-1RAcP complex from small-angle X-ray-scattering analysis resembles IL-1beta-IL-1RII-IL-1RAcP and IL-1beta-IL-1RI-IL-1RAcP crystal structures. The collective results confer IL-33 structure-function relationships, supporting and extending a general model for ligand-receptor assembly and activation in the IL-1 family.

Structural insights into the interaction of IL-33 with its receptors.,Liu X, Hammel M, He Y, Tainer JA, Jeng US, Zhang L, Wang S, Wang X Proc Natl Acad Sci U S A. 2013 Sep 10;110(37):14918-23. doi:, 10.1073/pnas.1308651110. Epub 2013 Aug 26. PMID:23980170^[15]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Schmitz J, Owyang A, Oldham E, Song Y, Murphy E, McClanahan TK, Zurawski G, Moshrefi M, Qin J, Li X, Gorman DM, Bazan JF, Kastelein RA. IL-33, an interleukin-1-like cytokine that signals via the IL-1 receptor-related protein ST2 and induces T helper type 2-associated cytokines. Immunity. 2005 Nov;23(5):479-90. PMID:16286016 doi:S1074-7613(05)00311-0
↑ Komai-Koma M, Xu D, Li Y, McKenzie AN, McInnes IB, Liew FY. IL-33 is a chemoattractant for human Th2 cells. Eur J Immunol. 2007 Oct;37(10):2779-86. PMID:17853410 doi:10.1002/eji.200737547
↑ Carriere V, Roussel L, Ortega N, Lacorre DA, Americh L, Aguilar L, Bouche G, Girard JP. IL-33, the IL-1-like cytokine ligand for ST2 receptor, is a chromatin-associated nuclear factor in vivo. Proc Natl Acad Sci U S A. 2007 Jan 2;104(1):282-7. Epub 2006 Dec 21. PMID:17185418 doi:10.1073/pnas.0606854104
↑ Kuchler AM, Pollheimer J, Balogh J, Sponheim J, Manley L, Sorensen DR, De Angelis PM, Scott H, Haraldsen G. Nuclear interleukin-33 is generally expressed in resting endothelium but rapidly lost upon angiogenic or proinflammatory activation. Am J Pathol. 2008 Oct;173(4):1229-42. doi: 10.2353/ajpath.2008.080014. Epub 2008 , Sep 11. PMID:18787100 doi:10.2353/ajpath.2008.080014
↑ Moussion C, Ortega N, Girard JP. The IL-1-like cytokine IL-33 is constitutively expressed in the nucleus of endothelial cells and epithelial cells in vivo: a novel 'alarmin'? PLoS One. 2008 Oct 6;3(10):e3331. doi: 10.1371/journal.pone.0003331. PMID:18836528 doi:10.1371/journal.pone.0003331
↑ Ali S, Mohs A, Thomas M, Klare J, Ross R, Schmitz ML, Martin MU. The dual function cytokine IL-33 interacts with the transcription factor NF-kappaB to dampen NF-kappaB-stimulated gene transcription. J Immunol. 2011 Aug 15;187(4):1609-16. doi: 10.4049/jimmunol.1003080. Epub 2011, Jul 6. PMID:21734074 doi:10.4049/jimmunol.1003080
↑ Kakkar R, Hei H, Dobner S, Lee RT. Interleukin 33 as a mechanically responsive cytokine secreted by living cells. J Biol Chem. 2012 Feb 24;287(9):6941-8. doi: 10.1074/jbc.M111.298703. Epub 2012, Jan 3. PMID:22215666 doi:10.1074/jbc.M111.298703
↑ Schmitz J, Owyang A, Oldham E, Song Y, Murphy E, McClanahan TK, Zurawski G, Moshrefi M, Qin J, Li X, Gorman DM, Bazan JF, Kastelein RA. IL-33, an interleukin-1-like cytokine that signals via the IL-1 receptor-related protein ST2 and induces T helper type 2-associated cytokines. Immunity. 2005 Nov;23(5):479-90. PMID:16286016 doi:S1074-7613(05)00311-0
↑ Komai-Koma M, Xu D, Li Y, McKenzie AN, McInnes IB, Liew FY. IL-33 is a chemoattractant for human Th2 cells. Eur J Immunol. 2007 Oct;37(10):2779-86. PMID:17853410 doi:10.1002/eji.200737547
↑ Carriere V, Roussel L, Ortega N, Lacorre DA, Americh L, Aguilar L, Bouche G, Girard JP. IL-33, the IL-1-like cytokine ligand for ST2 receptor, is a chromatin-associated nuclear factor in vivo. Proc Natl Acad Sci U S A. 2007 Jan 2;104(1):282-7. Epub 2006 Dec 21. PMID:17185418 doi:10.1073/pnas.0606854104
↑ Kuchler AM, Pollheimer J, Balogh J, Sponheim J, Manley L, Sorensen DR, De Angelis PM, Scott H, Haraldsen G. Nuclear interleukin-33 is generally expressed in resting endothelium but rapidly lost upon angiogenic or proinflammatory activation. Am J Pathol. 2008 Oct;173(4):1229-42. doi: 10.2353/ajpath.2008.080014. Epub 2008 , Sep 11. PMID:18787100 doi:10.2353/ajpath.2008.080014
↑ Moussion C, Ortega N, Girard JP. The IL-1-like cytokine IL-33 is constitutively expressed in the nucleus of endothelial cells and epithelial cells in vivo: a novel 'alarmin'? PLoS One. 2008 Oct 6;3(10):e3331. doi: 10.1371/journal.pone.0003331. PMID:18836528 doi:10.1371/journal.pone.0003331
↑ Ali S, Mohs A, Thomas M, Klare J, Ross R, Schmitz ML, Martin MU. The dual function cytokine IL-33 interacts with the transcription factor NF-kappaB to dampen NF-kappaB-stimulated gene transcription. J Immunol. 2011 Aug 15;187(4):1609-16. doi: 10.4049/jimmunol.1003080. Epub 2011, Jul 6. PMID:21734074 doi:10.4049/jimmunol.1003080
↑ Kakkar R, Hei H, Dobner S, Lee RT. Interleukin 33 as a mechanically responsive cytokine secreted by living cells. J Biol Chem. 2012 Feb 24;287(9):6941-8. doi: 10.1074/jbc.M111.298703. Epub 2012, Jan 3. PMID:22215666 doi:10.1074/jbc.M111.298703
↑ Liu X, Hammel M, He Y, Tainer JA, Jeng US, Zhang L, Wang S, Wang X. Structural insights into the interaction of IL-33 with its receptors. Proc Natl Acad Sci U S A. 2013 Sep 10;110(37):14918-23. doi:, 10.1073/pnas.1308651110. Epub 2013 Aug 26. PMID:23980170 doi:10.1073/pnas.1308651110

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4kc3"

Categories: Homo sapiens | Large Structures | Liu X | Wang XQ

@@ Line 1: / Line 1: @@
 ==Cytokine/receptor binary complex==
-<StructureSection load='4kc3' size='340' side='right' caption='[[4kc3]], [[Resolution|resolution]] 3.27&Aring;' scene=''>
+<StructureSection load='4kc3' size='340' side='right'caption='[[4kc3]], [[Resolution|resolution]] 3.27&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4kc3]] is a 2 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=4KC3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4KC3 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4kc3]] is a 2 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=4KC3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4KC3 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]] 3.2702&#8491;</td></tr>
-<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">IL33, C9orf26, IL1F11, NFHEV ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), IL1RL1, DER4, ST2, T1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=4kc3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4kc3 OCA], [https://pdbe.org/4kc3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4kc3 RCSB], [https://www.ebi.ac.uk/pdbsum/4kc3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4kc3 ProSAT]</span></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=4kc3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4kc3 OCA], [http://pdbe.org/4kc3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4kc3 RCSB], [http://www.ebi.ac.uk/pdbsum/4kc3 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4kc3 ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://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>  [[http://www.uniprot.org/uniprot/ILRL1_HUMAN ILRL1_HUMAN]] Receptor for interleukin-33 (IL-33), its stimulation recruits MYD88, IRAK1, IRAK4, and TRAF6, followed by phosphorylation of MAPK3/ERK1 and/or MAPK1/ERK2, MAPK14, and MAPK8. Possibly involved in helper T-cell function.<ref>PMID:16286016</ref>
+[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 ==
@@ Line 20: / Line 19: @@
 </div>
 <div class="pdbe-citations 4kc3" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Interleukin 3D structures|Interleukin 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
-[[Category: Liu, X]]
+[[Category: Large Structures]]
-[[Category: Wang, X Q]]
+[[Category: Liu X]]
-[[Category: Beta-trefoil]]
+[[Category: Wang XQ]]
-[[Category: Ig-like domain]]
-[[Category: Immune system]]

4kc3

From Proteopedia

Current revision

Cytokine/receptor binary complex

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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