3egb: Difference between revisions
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==Structure of Pellino2 FHA domain at 3.3 Angstroms resolution.== | ==Structure of Pellino2 FHA domain at 3.3 Angstroms resolution.== | ||
<StructureSection load='3egb' size='340' side='right' caption='[[3egb]], [[Resolution|resolution]] 3.25Å' scene=''> | <StructureSection load='3egb' size='340' side='right'caption='[[3egb]], [[Resolution|resolution]] 3.25Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[3egb]] is a 2 chain structure with sequence from [ | <table><tr><td colspan='2'>[[3egb]] 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=3EGB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3EGB FirstGlance]. <br> | ||
</td></tr><tr><td class="sblockLbl"><b>[[ | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.25Å</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=3egb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3egb OCA], [https://pdbe.org/3egb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3egb RCSB], [https://www.ebi.ac.uk/pdbsum/3egb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3egb ProSAT]</span></td></tr> | |||
<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | </table> | ||
<table> | == Function == | ||
[https://www.uniprot.org/uniprot/PELI2_HUMAN PELI2_HUMAN] E3 ubiquitin ligase catalyzing the covalent attachment of ubiquitin moieties onto substrate proteins. Involved in the TLR and IL-1 signaling pathways via interaction with the complex containing IRAK kinases and TRAF6. Mediates IL1B-induced IRAK1 'Lys-63'-linked polyubiquitination and possibly 'Lys-48'-linked ubiquitination. May be important for LPS- and IL1B-induced MAP3K7-dependent, but not MAP3K3-dependent, NF-kappa-B activation. Can activate the MAP (mitogen activated protein) kinase pathway leading to activation of ELK1.<ref>PMID:12804775</ref> <ref>PMID:12860405</ref> <ref>PMID:17675297</ref> <ref>PMID:17997719</ref> <ref>PMID:22669975</ref> | |||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
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Pellino proteins contain a cryptic FHA domain that mediates interaction with phosphorylated IRAK1.,Lin CC, Huoh YS, Schmitz KR, Jensen LE, Ferguson KM Structure. 2008 Dec 10;16(12):1806-16. PMID:19081057<ref>PMID:19081057</ref> | Pellino proteins contain a cryptic FHA domain that mediates interaction with phosphorylated IRAK1.,Lin CC, Huoh YS, Schmitz KR, Jensen LE, Ferguson KM Structure. 2008 Dec 10;16(12):1806-16. PMID:19081057<ref>PMID:19081057</ref> | ||
From | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | </div> | ||
<div class="pdbe-citations 3egb" style="background-color:#fffaf0;"></div> | |||
== References == | == References == | ||
<references/> | <references/> | ||
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</StructureSection> | </StructureSection> | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: | [[Category: Ferguson KM]] | ||
[[Category: | [[Category: Lin C]] | ||
[[Category: | [[Category: Schmitz KR]] | ||
Latest revision as of 16:02, 30 August 2023
Structure of Pellino2 FHA domain at 3.3 Angstroms resolution.Structure of Pellino2 FHA domain at 3.3 Angstroms resolution.
Structural highlights
FunctionPELI2_HUMAN E3 ubiquitin ligase catalyzing the covalent attachment of ubiquitin moieties onto substrate proteins. Involved in the TLR and IL-1 signaling pathways via interaction with the complex containing IRAK kinases and TRAF6. Mediates IL1B-induced IRAK1 'Lys-63'-linked polyubiquitination and possibly 'Lys-48'-linked ubiquitination. May be important for LPS- and IL1B-induced MAP3K7-dependent, but not MAP3K3-dependent, NF-kappa-B activation. Can activate the MAP (mitogen activated protein) kinase pathway leading to activation of ELK1.[1] [2] [3] [4] [5] Publication Abstract from PubMedPellino proteins are RING E3 ubiquitin ligases involved in signaling events downstream of the Toll and interleukin-1 (IL-1) receptors, key initiators of innate immune and inflammatory responses. Pellino proteins associate with and ubiquitinate proteins in these pathways, including the interleukin-1 receptor associated kinase-1 (IRAK1). We determined the X-ray crystal structure of a Pellino2 fragment lacking only the RING domain. This structure reveals that the IRAK1-binding region of Pellino proteins consists largely of a previously unidentified forkhead-associated (FHA) domain. FHA domains are well-characterized phosphothreonine-binding modules, and this cryptic example in Pellino2 can drive interaction of this protein with phosphorylated IRAK1. The Pellino FHA domain is decorated with an unusual appendage or "wing" composed of two long inserts that lie within the FHA homology region. Delineating how this E3 ligase associates with substrates, and how these interactions are regulated by phosphorylation, is crucial for a complete understanding of Toll/IL-1 receptor signaling. Pellino proteins contain a cryptic FHA domain that mediates interaction with phosphorylated IRAK1.,Lin CC, Huoh YS, Schmitz KR, Jensen LE, Ferguson KM Structure. 2008 Dec 10;16(12):1806-16. PMID:19081057[6] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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