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==NMR structure of monomeric human IRAK-M Death Domain R56D, Y61E mutant== | ==NMR structure of monomeric human IRAK-M Death Domain R56D, Y61E mutant== | ||
<StructureSection load='5uke' size='340' side='right' caption='[[5uke]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | <StructureSection load='5uke' size='340' side='right'caption='[[5uke]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[5uke]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5UKE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5UKE FirstGlance]. <br> | <table><tr><td colspan='2'>[[5uke]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5UKE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5UKE FirstGlance]. <br> | ||
</td></tr><tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </span></td></tr> | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">IRAK3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | ||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </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=5uke FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5uke OCA], [http://pdbe.org/5uke PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5uke RCSB], [http://www.ebi.ac.uk/pdbsum/5uke PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5uke 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=5uke FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5uke OCA], [http://pdbe.org/5uke PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5uke RCSB], [http://www.ebi.ac.uk/pdbsum/5uke PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5uke ProSAT]</span></td></tr> | ||
</table> | </table> | ||
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== Function == | == Function == | ||
[[http://www.uniprot.org/uniprot/IRAK3_HUMAN IRAK3_HUMAN]] Inhibits dissociation of IRAK1 and IRAK4 from the Toll-like receptor signaling complex by either inhibiting the phosphorylation of IRAK1 and IRAK4 or stabilizing the receptor complex.[UniProtKB:Q8K4B2]<ref>PMID:10383454</ref> | [[http://www.uniprot.org/uniprot/IRAK3_HUMAN IRAK3_HUMAN]] Inhibits dissociation of IRAK1 and IRAK4 from the Toll-like receptor signaling complex by either inhibiting the phosphorylation of IRAK1 and IRAK4 or stabilizing the receptor complex.[UniProtKB:Q8K4B2]<ref>PMID:10383454</ref> | ||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Interleukin 33 (IL-33) is among the earliest-released cytokines in response to allergens that orchestrate type 2 immunity. The prolyl cis-trans isomerase PIN1 is known to induce cytokines for eosinophil survival and activation by stabilizing cytokines mRNAs, but the function of PIN1 in upstream signaling pathways in asthma is unknown. Here we show that interleukin receptor associated kinase M (IRAK-M) is a PIN1 target critical for IL-33 signaling in allergic asthma. NMR analysis and docking simulations suggest that PIN1 might regulate IRAK-M conformation and function in IL-33 signaling. Upon IL-33-induced airway inflammation, PIN1 is activated for binding with and isomerization of IRAK-M, resulting in IRAK-M nuclear translocation and induction of selected proinflammatory genes in dendritic cells. Thus, the IL-33-PIN1-IRAK-M is an axis critical for dendritic cell activation, type 2 immunity and IL-33 induced airway inflammation. | |||
The IL-33-PIN1-IRAK-M axis is critical for type 2 immunity in IL-33-induced allergic airway inflammation.,Nechama M, Kwon J, Wei S, Kyi AT, Welner RS, Ben-Dov IZ, Arredouani MS, Asara JM, Chen CH, Tsai CY, Nelson KF, Kobayashi KS, Israel E, Zhou XZ, Nicholson LK, Lu KP Nat Commun. 2018 Apr 23;9(1):1603. doi: 10.1038/s41467-018-03886-6. PMID:29686383<ref>PMID:29686383</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 5uke" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Interleukin-1 receptor-associated kinase|Interleukin-1 receptor-associated kinase]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Human]] | |||
[[Category: Large Structures]] | |||
[[Category: Non-specific serine/threonine protein kinase]] | [[Category: Non-specific serine/threonine protein kinase]] | ||
[[Category: Kwon, J]] | [[Category: Kwon, J]] | ||
Revision as of 12:29, 4 December 2019
NMR structure of monomeric human IRAK-M Death Domain R56D, Y61E mutantNMR structure of monomeric human IRAK-M Death Domain R56D, Y61E mutant
Structural highlights
Disease[IRAK3_HUMAN] Disease susceptibility is associated with variations affecting the gene represented in this entry. Function[IRAK3_HUMAN] Inhibits dissociation of IRAK1 and IRAK4 from the Toll-like receptor signaling complex by either inhibiting the phosphorylation of IRAK1 and IRAK4 or stabilizing the receptor complex.[UniProtKB:Q8K4B2][1] Publication Abstract from PubMedInterleukin 33 (IL-33) is among the earliest-released cytokines in response to allergens that orchestrate type 2 immunity. The prolyl cis-trans isomerase PIN1 is known to induce cytokines for eosinophil survival and activation by stabilizing cytokines mRNAs, but the function of PIN1 in upstream signaling pathways in asthma is unknown. Here we show that interleukin receptor associated kinase M (IRAK-M) is a PIN1 target critical for IL-33 signaling in allergic asthma. NMR analysis and docking simulations suggest that PIN1 might regulate IRAK-M conformation and function in IL-33 signaling. Upon IL-33-induced airway inflammation, PIN1 is activated for binding with and isomerization of IRAK-M, resulting in IRAK-M nuclear translocation and induction of selected proinflammatory genes in dendritic cells. Thus, the IL-33-PIN1-IRAK-M is an axis critical for dendritic cell activation, type 2 immunity and IL-33 induced airway inflammation. The IL-33-PIN1-IRAK-M axis is critical for type 2 immunity in IL-33-induced allergic airway inflammation.,Nechama M, Kwon J, Wei S, Kyi AT, Welner RS, Ben-Dov IZ, Arredouani MS, Asara JM, Chen CH, Tsai CY, Nelson KF, Kobayashi KS, Israel E, Zhou XZ, Nicholson LK, Lu KP Nat Commun. 2018 Apr 23;9(1):1603. doi: 10.1038/s41467-018-03886-6. PMID:29686383[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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