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< | ==Solution structure of the DEATH domain of Interleukin-1 receptor-associated kinase4 (IRAK4) from Mus musculus== | ||
<StructureSection load='1wh4' size='340' side='right'caption='[[1wh4]]' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[1wh4]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1WH4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1WH4 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=1wh4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1wh4 OCA], [https://pdbe.org/1wh4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1wh4 RCSB], [https://www.ebi.ac.uk/pdbsum/1wh4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1wh4 ProSAT], [https://www.topsan.org/Proteins/RSGI/1wh4 TOPSAN]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/IRAK4_MOUSE IRAK4_MOUSE] Serine/threonine-protein kinase that plays a critical role in initiating innate immune response against foreign pathogens. Involved in Toll-like receptor (TLR) and IL-1R signaling pathways. Is rapidly recruited by MYD88 to the receptor-signaling complex upon TLR activation to form the Myddosome together with IRAK2. Phosphorylates initially IRAK1, thus stimulating the kinase activity and intensive autophosphorylation of IRAK1. Phosphorylates E3 ubiquitin ligases Pellino proteins (PELI1, PELI2 and PELI3) to promote pellino-mediated polyubiquitination of IRAK1. Then, the ubiquitin-binding domain of IKBKG/NEMO binds to polyubiquitinated IRAK1 bringing together the IRAK1-MAP3K7/TAK1-TRAF6 complex and the NEMO-IKKA-IKKB complex. In turn, MAP3K7/TAK1 activates IKKs (CHUK/IKKA and IKBKB/IKKB) leading to NF-kappa-B nuclear translocation and activation. Alternatively, phosphorylates TIRAP to promote its ubiquitination and subsequent degradation. Phosphorylates NCF1 and regulates NADPH oxidase activation after LPS stimulation suggesting a similar mechanism during microbial infections (By similarity). | |||
== 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/wh/1wh4_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/main_output.php?pdb_ID=1wh4 ConSurf]. | |||
<div style="clear:both"></div> | |||
=== | ==See Also== | ||
*[[Interleukin-1 receptor-associated kinase|Interleukin-1 receptor-associated kinase]] | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Mus musculus]] | [[Category: Mus musculus]] | ||
[[Category: Kigawa T]] | |||
[[Category: Koshiba S]] | |||
[[Category: Kigawa | [[Category: Nameki N]] | ||
[[Category: Koshiba | [[Category: Tomizawa T]] | ||
[[Category: Nameki | [[Category: Yokoyama S]] | ||
[[Category: Tomizawa | |||
[[Category: Yokoyama | |||
Latest revision as of 16:38, 9 May 2024
Solution structure of the DEATH domain of Interleukin-1 receptor-associated kinase4 (IRAK4) from Mus musculusSolution structure of the DEATH domain of Interleukin-1 receptor-associated kinase4 (IRAK4) from Mus musculus
Structural highlights
FunctionIRAK4_MOUSE Serine/threonine-protein kinase that plays a critical role in initiating innate immune response against foreign pathogens. Involved in Toll-like receptor (TLR) and IL-1R signaling pathways. Is rapidly recruited by MYD88 to the receptor-signaling complex upon TLR activation to form the Myddosome together with IRAK2. Phosphorylates initially IRAK1, thus stimulating the kinase activity and intensive autophosphorylation of IRAK1. Phosphorylates E3 ubiquitin ligases Pellino proteins (PELI1, PELI2 and PELI3) to promote pellino-mediated polyubiquitination of IRAK1. Then, the ubiquitin-binding domain of IKBKG/NEMO binds to polyubiquitinated IRAK1 bringing together the IRAK1-MAP3K7/TAK1-TRAF6 complex and the NEMO-IKKA-IKKB complex. In turn, MAP3K7/TAK1 activates IKKs (CHUK/IKKA and IKBKB/IKKB) leading to NF-kappa-B nuclear translocation and activation. Alternatively, phosphorylates TIRAP to promote its ubiquitination and subsequent degradation. Phosphorylates NCF1 and regulates NADPH oxidase activation after LPS stimulation suggesting a similar mechanism during microbial infections (By similarity). Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. See Also |
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