7pdj
From Proteopedia
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==R12E vFLIP mutant== | ==R12E vFLIP mutant== | ||
| - | <StructureSection load='7pdj' size='340' side='right'caption='[[7pdj]]' scene=''> | + | <StructureSection load='7pdj' size='340' side='right'caption='[[7pdj]], [[Resolution|resolution]] 4.20Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7PDJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7PDJ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7pdj]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Human_gammaherpesvirus_8 Human gammaherpesvirus 8]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7PDJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7PDJ FirstGlance]. <br> |
</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=7pdj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7pdj OCA], [https://pdbe.org/7pdj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7pdj RCSB], [https://www.ebi.ac.uk/pdbsum/7pdj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7pdj ProSAT]</span></td></tr> | </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=7pdj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7pdj OCA], [https://pdbe.org/7pdj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7pdj RCSB], [https://www.ebi.ac.uk/pdbsum/7pdj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7pdj ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/VFLIP_HHV8P VFLIP_HHV8P] Plays a role in the modulation of host signaling pathways by acting as an activator of both the classic and the alternative NF-kappa-B pathways. Thereby, initiates an important range of cellular processes to promote cell survival, proliferation and protection from apoptosis.<ref>PMID:10523854</ref> <ref>PMID:16311516</ref> <ref>PMID:29698475</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Constitutive activation of the canonical NF-kappaB signaling pathway is a major factor in Kaposi's sarcoma-associated herpes virus pathogenesis where it is essential for the survival of primary effusion lymphoma. Central to this process is persistent upregulation of the inhibitor of kappaB kinase (IKK) complex by the virally encoded oncoprotein vFLIP. Although the physical interaction between vFLIP and the IKK kinase regulatory component essential for persistent activation, IKKgamma, has been well characterized, it remains unclear how the kinase subunits are rendered active mechanistically. Using a combination of cell-based assays, biophysical techniques, and structural biology, we demonstrate here that vFLIP alone is sufficient to activate the IKK kinase complex. Furthermore, we identify weakly stabilized, high molecular weight vFLIP-IKKgamma assemblies that are key to the activation process. Taken together, our results are the first to reveal that vFLIP-induced NF-kappaB activation pivots on the formation of structurally specific vFLIP-IKKgamma multimers which have an important role in rendering the kinase subunits active through a process of autophosphorylation. This mechanism of NF-kappaB activation is in contrast to those utilized by endogenous cytokines and cellular FLIP homologues. | ||
| + | |||
| + | Mechanistic insights into the activation of the IKK kinase complex by the Kaposi's sarcoma herpes virus oncoprotein vFLIP.,Bagneris C, Senthil Kumar SL, Baratchian M, Britt HM, Assafa TE, Thalassinos K, Collins MK, Barrett TE J Biol Chem. 2022 Jun;298(6):102012. doi: 10.1016/j.jbc.2022.102012. Epub 2022 , May 5. PMID:35525271<ref>PMID:35525271</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 7pdj" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Human gammaherpesvirus 8]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Barrett TE]] | [[Category: Barrett TE]] | ||
Revision as of 12:53, 22 February 2023
R12E vFLIP mutant
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